rs3744565

chr17-10531608-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017534.6(MYH2):c.2697+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,613,758 control chromosomes in the GnomAD database, including 155,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13792 hom., cov: 32)
  • Exomes 𝑓: 0.43 (142020 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.280

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-10531608-T-C is Benign according to our data. Variant chr17-10531608-T-C is described in ClinVar as [Benign]. Clinvar id is 260818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH2	NM_017534.6	c.2697+25A>G		intron_variant		ENST00000245503.10
MYHAS	NR_125367.1	n.168-35929T>C		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.2697+25A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH2	ENST00000245503.10	c.2697+25A>G		intron_variant		1	NM_017534.6	P1
	ENST00000399342.6	n.207-1716T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62519 AN: 151952 Hom.: 13781 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.408

GnomAD3 exomes AF: 0.487 AC: 121864 AN: 250400 Hom.: 32125 AF XY: 0.486 AC XY: 65893 AN XY: 135474

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.849

Gnomad SAS exome AF: 0.596

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.430 AC: 628817 AN: 1461688 Hom.: 142020 Cov.: 50 AF XY: 0.434 AC XY: 315863 AN XY: 727156

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.831

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.411 AC: 62564 AN: 152070 Hom.: 13792 Cov.: 32 AF XY: 0.424 AC XY: 31487 AN XY: 74344

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.407

Alfa AF: 0.413 Hom.: 13468

Bravo AF: 0.408

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Myopathy, proximal, and ophthalmoplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.0
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs3744565; hg19: chr17-10434925; COSMIC: COSV55434331;