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. The variant received -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
• Publications: 27 publications found

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]

MYH7B Gene-Disease associations (from GenCC):

• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020884.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	NM_020884.7	MANE Select	c.2451G>A	p.Ala817Ala	synonymous	Exon 27 of 45	NP_065935.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.2451G>A	p.Ala817Ala	synonymous	Exon 27 of 45	ENSP00000262873.8
	MYH7B	ENST00000888939.1		c.2415G>A	p.Ala805Ala	synonymous	Exon 22 of 40	ENSP00000558998.1
	MYH7B	ENST00000971120.1		c.2415G>A	p.Ala805Ala	synonymous	Exon 23 of 41	ENSP00000641179.1

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

GnomAD2 exomes AF: 0.448 AC: 111056 AN: 247938 AF XY: 0.435

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 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

African (AFR) AF: 0.204 AC: 6831 AN: 33458

American (AMR) AF: 0.700 AC: 31294 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 10025 AN: 26128

East Asian (EAS) AF: 0.558 AC: 22136 AN: 39664

South Asian (SAS) AF: 0.301 AC: 25946 AN: 86230

European-Finnish (FIN) AF: 0.460 AC: 24158 AN: 52530

Middle Eastern (MID) AF: 0.406 AC: 2340 AN: 5766

European-Non Finnish (NFE) AF: 0.433 AC: 480802 AN: 1111322

Other (OTH) AF: 0.422 AC: 25437 AN: 60344

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

African (AFR) AF: 0.218 AC: 9047 AN: 41536

American (AMR) AF: 0.563 AC: 8613 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2828 AN: 5178

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4826

European-Finnish (FIN) AF: 0.469 AC: 4962 AN: 10588

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29863 AN: 67988

Other (OTH) AF: 0.424 AC: 896 AN: 2114

Alfa AF: 0.419 Hom.: 37112

Bravo AF: 0.399

Asia WGS AF: 0.400 AC: 1390 AN: 3478

EpiCase AF: 0.438

EpiControl AF: 0.435

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MYH7B-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-0.82
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2425012; hg19: chr20-33581955; COSMIC: COSV53419994; COSMIC: COSV53419994;