rs2288206

Variant names:

• chr2-151560550-G-A
• rs2288206
• NM_001164507.2:c.19314+42C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-151560550-G-A
• chr2-151560550-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001164507.2(NEB):​c.19314+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6392 hom., cov: 27)
  • Exomes 𝑓: 0.26 (45134 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEB NM_001164507.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.447
• Publications: 6 publications found

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB Gene-Disease associations (from GenCC):

• nemaline myopathy 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
• childhood-onset nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intermediate nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• typical nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• severe congenital nemaline myopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-151560550-G-A is Benign according to our data. Variant chr2-151560550-G-A is described in ClinVar as Benign. ClinVar VariationId is 257779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2	c.19314+42C>T		intron_variant	Intron 124 of 181	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2	c.19314+42C>T		intron_variant	Intron 124 of 181	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8	c.19314+42C>T		intron_variant	Intron 124 of 181	5	NM_001164508.2	ENSP00000380505.3
NEB	ENST00000427231.7	c.19314+42C>T		intron_variant	Intron 124 of 181	5	NM_001164507.2	ENSP00000416578.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42660 AN: 150794 Hom.: 6387 Cov.: 27

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.283

GnomAD2 exomes AF: 0.295 AC: 49242 AN: 166744 AF XY: 0.286

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.336

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.306

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.259 AC: 332874 AN: 1284046 Hom.: 45134 Cov.: 19 AF XY: 0.257 AC XY: 164443 AN XY: 640206

African (AFR) AF: 0.313 AC: 9236 AN: 29470

American (AMR) AF: 0.397 AC: 14566 AN: 36716

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5672 AN: 24470

East Asian (EAS) AF: 0.357 AC: 12844 AN: 35996

South Asian (SAS) AF: 0.185 AC: 14240 AN: 77168

European-Finnish (FIN) AF: 0.289 AC: 14305 AN: 49524

Middle Eastern (MID) AF: 0.304 AC: 1402 AN: 4614

European-Non Finnish (NFE) AF: 0.253 AC: 245972 AN: 971884

Other (OTH) AF: 0.270 AC: 14637 AN: 54204

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.283 AC: 42694 AN: 150912 Hom.: 6392 Cov.: 27 AF XY: 0.284 AC XY: 20920 AN XY: 73662

African (AFR) AF: 0.306 AC: 12558 AN: 41078

American (AMR) AF: 0.383 AC: 5774 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 822 AN: 3460

East Asian (EAS) AF: 0.326 AC: 1653 AN: 5076

South Asian (SAS) AF: 0.176 AC: 838 AN: 4766

European-Finnish (FIN) AF: 0.273 AC: 2854 AN: 10438

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17215 AN: 67746

Other (OTH) AF: 0.280 AC: 583 AN: 2080

Alfa AF: 0.267 Hom.: 942

Bravo AF: 0.297

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nemaline myopathy 2 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis multiplex congenita 6 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: 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	-0.82
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		0.45
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: rs2288206; hg19: chr2-152417064; COSMIC: COSV50807678;