Variant 17-10539165-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017534.6(MYH2):c.1416+40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,613,596 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 8 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0100

Variant links:

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]

MYH2 links:

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]

MYHAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-10539165-C-G is Benign according to our data. Variant chr17-10539165-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000992 (151/152204) while in subpopulation EAS AF= 0.0166 (86/5174). AF 95% confidence interval is 0.0138. There are 1 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.1416+40G>C	intron_variant	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.1416+40G>C	intron_variant		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-28372C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.1416+40G>C		intron_variant		1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0170

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00266

AC:

667

AN:

251170

Hom.:

AF XY:

0.00220

AC XY:

299

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00789

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0177

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.000616

AC:

900

AN:

1461392

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

393

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00718

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00924

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000992

AC:

151

AN:

152204

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.00156

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.0

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over