rs2277652

Variant names:

• chr17-10529532-G-A
• rs2277652
• NM_017534.6:c.3117+32C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017534.6(MYH2):​c.3117+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,614,102 control chromosomes in the GnomAD database, including 3,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (350 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2916 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00700
• Publications: 4 publications found

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-10529532-G-A is Benign according to our data. Variant chr17-10529532-G-A is described in ClinVar as [Benign]. Clinvar id is 260820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6	c.3117+32C>T		intron_variant	Intron 24 of 39	ENST00000245503.10	NP_060004.3
MYH2	NM_001100112.2	c.3117+32C>T		intron_variant	Intron 24 of 39		NP_001093582.1
MYHAS	NR_125367.1	n.168-38005G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.3117+32C>T		intron_variant	Intron 24 of 39	1	NM_017534.6	ENSP00000245503.5

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9648 AN: 152098 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.0284

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0740

GnomAD2 exomes AF: 0.0598 AC: 15041 AN: 251448 AF XY: 0.0629

Gnomad AFR exome AF: 0.0821

Gnomad AMR exome AF: 0.0370

Gnomad ASJ exome AF: 0.0815

Gnomad EAS exome AF: 0.0226

Gnomad FIN exome AF: 0.0544

Gnomad NFE exome AF: 0.0549

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0589 AC: 86036 AN: 1461888 Hom.: 2916 Cov.: 35 AF XY: 0.0604 AC XY: 43952 AN XY: 727244

African (AFR) AF: 0.0824 AC: 2758 AN: 33480

American (AMR) AF: 0.0382 AC: 1707 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2134 AN: 26136

East Asian (EAS) AF: 0.0284 AC: 1129 AN: 39700

South Asian (SAS) AF: 0.110 AC: 9526 AN: 86256

European-Finnish (FIN) AF: 0.0537 AC: 2867 AN: 53420

Middle Eastern (MID) AF: 0.0586 AC: 338 AN: 5768

European-Non Finnish (NFE) AF: 0.0556 AC: 61813 AN: 1112008

Other (OTH) AF: 0.0623 AC: 3764 AN: 60396

GnomAD4 genome AF: 0.0637 AC: 9690 AN: 152214 Hom.: 350 Cov.: 32 AF XY: 0.0646 AC XY: 4809 AN XY: 74402

African (AFR) AF: 0.0806 AC: 3347 AN: 41550

American (AMR) AF: 0.0460 AC: 703 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3468

East Asian (EAS) AF: 0.0285 AC: 147 AN: 5158

South Asian (SAS) AF: 0.122 AC: 587 AN: 4808

European-Finnish (FIN) AF: 0.0527 AC: 558 AN: 10590

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0565 AC: 3846 AN: 68020

Other (OTH) AF: 0.0728 AC: 154 AN: 2116

Alfa AF: 0.0590 Hom.: 40

Bravo AF: 0.0619

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.84
CADD	Benign	11
DANN	Benign	0.48
PhyloP100		-0.0070
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: rs2277652; hg19: chr17-10432849; COSMIC: COSV55439170;