17-10535412-T-C

Variant names:

• chr17-10535412-T-C
• rs3744567
• NM_017534.6:c.1975-47A>G

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:3
• 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]

ENSG00000272736 (HGNC:):

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
MYH2	NM_017534.6	c.1975-47A>G		intron_variant	Intron 17 of 39	ENST00000245503.10	NP_060004.3
MYH2	NM_001100112.2	c.1975-47A>G		intron_variant	Intron 17 of 39		NP_001093582.1
MYHAS	NR_125367.1	n.168-32125T>C		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.1975-47A>G		intron_variant	Intron 17 of 39	1	NM_017534.6	ENSP00000245503.5

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:3

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

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;