chr11-1934874-T-C

Variant names:

• chr11-1934874-T-C
• rs16927166
• NM_006757.4:c.636T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006757.4(TNNT3):​c.636T>C​(p.Ile212Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,613,608 control chromosomes in the GnomAD database, including 675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (253 hom., cov: 33)
  • Exomes 𝑓: 0.015 (422 hom.)
• Consequence: TNNT3 NM_006757.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.99
• Publications: 7 publications found

Genes affected

TNNT3 (HGNC:11950): (troponin T3, fast skeletal type) The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]

TNNT3 Gene-Disease associations (from GenCC):

• distal arthrogryposis type 2B1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: STRONG Submitted by: G2P
• arthrogryposis, distal, type 2B2

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• nemaline myopathy

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sheldon-hall syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-1934874-T-C is Benign according to our data. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT3	NM_006757.4	c.636T>C	p.Ile212Ile	synonymous_variant	Exon 14 of 16	ENST00000278317.11	NP_006748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT3	ENST00000278317.11	c.636T>C	p.Ile212Ile	synonymous_variant	Exon 14 of 16	5	NM_006757.4	ENSP00000278317.6

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5870 AN: 152182 Hom.: 251 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0316

GnomAD2 exomes AF: 0.0210 AC: 5280 AN: 251284 AF XY: 0.0212

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0133

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00473

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.0188

GnomAD4 exome AF: 0.0148 AC: 21577 AN: 1461308 Hom.: 422 Cov.: 33 AF XY: 0.0154 AC XY: 11230 AN XY: 726932

African (AFR) AF: 0.102 AC: 3403 AN: 33476

American (AMR) AF: 0.0141 AC: 629 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00585 AC: 153 AN: 26136

East Asian (EAS) AF: 0.00254 AC: 101 AN: 39700

South Asian (SAS) AF: 0.0450 AC: 3884 AN: 86258

European-Finnish (FIN) AF: 0.00445 AC: 235 AN: 52856

Middle Eastern (MID) AF: 0.0354 AC: 204 AN: 5768

European-Non Finnish (NFE) AF: 0.0106 AC: 11802 AN: 1112002

Other (OTH) AF: 0.0193 AC: 1166 AN: 60388

GnomAD4 genome AF: 0.0387 AC: 5890 AN: 152300 Hom.: 253 Cov.: 33 AF XY: 0.0383 AC XY: 2850 AN XY: 74482

African (AFR) AF: 0.103 AC: 4272 AN: 41560

American (AMR) AF: 0.0244 AC: 373 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3466

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5184

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4830

European-Finnish (FIN) AF: 0.00744 AC: 79 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 830 AN: 68014

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.0185 Hom.: 179

Bravo AF: 0.0413

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.0132

EpiControl AF: 0.0146

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3 Other:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 18, 2012

Leiden Muscular Dystrophy (TNNT3)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Nov 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Distal arthrogryposis type 2B1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Arthrogryposis multiplex congenita distal Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.52
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16927166; hg19: chr11-1956104; COSMIC: COSV53485438; COSMIC: COSV53485438;