NM_003289.4:c.564-19dupC

Variant names:

• chr9-35684825-C-CG
• rs3215700
• NM_003289.4:c.564-19dupC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003289.4(TPM2):​c.564-19dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,596,748 control chromosomes in the GnomAD database, including 303,763 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29446 hom., cov: 0)
  • Exomes 𝑓: 0.62 (274317 hom.)
• Consequence: TPM2 NM_003289.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.39

Genes affected

TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-35684825-C-CG is Benign according to our data. Variant chr9-35684825-C-CG is described in ClinVar as [Benign]. Clinvar id is 94123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM2	NM_003289.4	c.564-19dupC		intron_variant	Intron 5 of 8	ENST00000645482.3	NP_003280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3	c.564-19dupC		intron_variant	Intron 5 of 8		NM_003289.4	ENSP00000496494.2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 93834 AN: 150344 Hom.: 29415 Cov.: 0

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.618 AC: 893752 AN: 1446288 Hom.: 274317 Cov.: 36 AF XY: 0.620 AC XY: 446208 AN XY: 719346

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.624 AC: 93917 AN: 150460 Hom.: 29446 Cov.: 0 AF XY: 0.629 AC XY: 46210 AN XY: 73418

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.645

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Feb 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 18, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Arthrogryposis, distal, type 1A Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3215700; hg19: chr9-35684822;