rs145796634

chr17-10529633-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_017534.6(MYH2):c.3048G>A(p.Leu1016=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,614,140 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (3 hom.)
• Consequence: MYH2 NM_017534.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.868

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-10529633-C-T is Benign according to our data. Variant chr17-10529633-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.868 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH2	NM_017534.6	c.3048G>A	p.Leu1016=	synonymous_variant	24/40	ENST00000245503.10
MYHAS	NR_125367.1	n.168-37904C>T		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.3048G>A	p.Leu1016=	synonymous_variant	24/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH2	ENST00000245503.10	c.3048G>A	p.Leu1016=	synonymous_variant	24/40	1	NM_017534.6	P1
	ENST00000399342.6	n.207-3691C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00109 AC: 275 AN: 251430 Hom.: 0 AF XY: 0.00120 AC XY: 163 AN XY: 135892

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000827

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000734 AC: 1073 AN: 1461892 Hom.: 3 Cov.: 34 AF XY: 0.000800 AC XY: 582 AN XY: 727248

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00471

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00235

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000491

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00112 AC: 170 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74448

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00106

EpiCase AF: 0.00196

EpiControl AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	MYH2: BP4, BP7 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Myopathy, proximal, and ophthalmoplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	4.0
Dann	Benign	0.76

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: rs145796634; hg19: chr17-10432950; COSMIC: COSV55445170;