rs3744567

chr17-10535412-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.1975-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,481,808 control chromosomes in the GnomAD database, including 2,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (249 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2542 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.136

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=-0.82).
• BP6: Variant 17-10535412-T-C is Benign according to our data. Variant chr17-10535412-T-C is described in ClinVar as [Benign]. Clinvar id is 260815.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/exons	MANE	UniProt
MYH2	NM_017534.6	c.1975-47A>G		intron_variant		ENST00000245503.10
MYHAS	NR_125367.1	n.168-32125T>C		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.1975-47A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH2	ENST00000245503.10	c.1975-47A>G		intron_variant		1	NM_017534.6	P1
	ENST00000399342.6	n.370+1925T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8167 AN: 152132 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0670

GnomAD3 exomes AF: 0.0576 AC: 13829 AN: 240158 Hom.: 488 AF XY: 0.0614 AC XY: 7968 AN XY: 129742

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.0828

Gnomad EAS exome AF: 0.0228

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0578 AC: 76862 AN: 1329558 Hom.: 2542 Cov.: 21 AF XY: 0.0597 AC XY: 39871 AN XY: 667994

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.0286

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0605

GnomAD4 genome AF: 0.0537 AC: 8183 AN: 152250 Hom.: 249 Cov.: 32 AF XY: 0.0552 AC XY: 4106 AN XY: 74438

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0547 Hom.: 35

Bravo AF: 0.0507

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

-

- -

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	-0.82
Cadd	Benign	1.4
Dann	Benign	0.61

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: rs3744567; hg19: chr17-10438729;