rs2425012

Variant names:

• chr20-34994152-G-A
• rs2425012
• NM_020884.7:c.2451G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34994152-G-A
• chr20-34994152-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_020884.7(MYH7B):​c.2451G>A​(p.Ala817Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,340 control chromosomes in the GnomAD database, including 152,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12856 hom., cov: 34)
  • Exomes 𝑓: 0.43 (139658 hom.)
• Consequence: MYH7B NM_020884.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.820

Genes affected

MYH7B (HGNC:15906): (myosin heavy chain 7B) The myosin II molecule is a multi-subunit complex consisting of two heavy chains and four light chains. This gene encodes a heavy chain of myosin II, which is a member of the motor-domain superfamily. The heavy chain includes a globular motor domain, which catalyzes ATP hydrolysis and interacts with actin, and a tail domain in which heptad repeat sequences promote dimerization by interacting to form a rod-like alpha-helical coiled coil. This heavy chain subunit is a slow-twitch myosin. Alternatively spliced transcript variants have been found, but the full-length nature of these variants is not determined. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 20-34994152-G-A is Benign according to our data. Variant chr20-34994152-G-A is described in ClinVar as [Benign]. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.2451G>A	p.Ala817Ala	synonymous_variant	Exon 27 of 45	ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.2451G>A	p.Ala817Ala	synonymous_variant	Exon 27 of 45	1	NM_020884.7	ENSP00000262873.8

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59609 AN: 152088 Hom.: 12831 Cov.: 34

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.448 AC: 111056 AN: 247938 Hom.: 27229 AF XY: 0.435 AC XY: 58604 AN XY: 134678

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.718

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.516

Gnomad SAS exome AF: 0.299

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.431 AC: 628969 AN: 1460134 Hom.: 139658 Cov.: 53 AF XY: 0.427 AC XY: 309922 AN XY: 726198

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.392 AC: 59658 AN: 152206 Hom.: 12856 Cov.: 34 AF XY: 0.395 AC XY: 29406 AN XY: 74402

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.424

Alfa AF: 0.428 Hom.: 22181

Bravo AF: 0.399

Asia WGS AF: 0.400 AC: 1390 AN: 3478

EpiCase AF: 0.438

EpiControl AF: 0.435

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Dec 27, 2017

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. -

MYH7B-related disorder Benign:1

Jun 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	10
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2425012; hg19: chr20-33581955; COSMIC: COSV53419994; COSMIC: COSV53419994;