17-10535374-C-T

Position:

chr17-10535374-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017534.6(MYH2):c.1975-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,611,432 control chromosomes in the GnomAD database, including 3,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 356 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2944 hom. )

Consequence

MYH2
NM_017534.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002611

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.93

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:

(HGNC:):

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=-0.67).

BP6

Variant 17-10535374-C-T is Benign according to our data. Variant chr17-10535374-C-T is described in ClinVar as [Benign]. Clinvar id is 260816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10535374-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH2	NM_017534.6 linkuse as main transcript	c.1975-9G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000245503.10
MYHAS	NR_125367.1 linkuse as main transcript	n.168-32163C>T	intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2 linkuse as main transcript	c.1975-9G>A	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.1975-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017534.6	P1	Q9UKX2-1
	ENST00000399342.6 linkuse as main transcript	n.370+1887C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9803

AN:

152018

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0488

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.0458

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0525

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0566

Gnomad OTH

AF:

0.0761

GnomAD3 exomes

AF:

0.0625

AC:

15663

AN:

250592

Hom.:

592

AF XY:

0.0652

AC XY:

8830

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0828

Gnomad EAS exome

AF:

0.0404

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0544

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0602

GnomAD4 exome

AF:

0.0594

AC:

86662

AN:

1459296

Hom.:

2944

Cov.:

AF XY:

0.0609

AC XY:

44219

AN XY:

726134

show subpopulations

Gnomad4 AFR exome

AF:

0.0824

Gnomad4 AMR exome

AF:

0.0453

Gnomad4 ASJ exome

AF:

0.0830

Gnomad4 EAS exome

AF:

0.0377

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0537

Gnomad4 NFE exome

AF:

0.0554

Gnomad4 OTH exome

AF:

0.0639

GnomAD4 genome

AF:

0.0647

AC:

9846

AN:

152136

Hom.:

356

Cov.:

AF XY:

0.0657

AC XY:

4888

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.0487

Gnomad4 ASJ

AF:

0.0804

Gnomad4 EAS

AF:

0.0455

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0525

Gnomad4 NFE

AF:

0.0566

Gnomad4 OTH

AF:

0.0762

Alfa

AF:

0.0563

Hom.:

384

Bravo

AF:

0.0635

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Myopathy, proximal, and ophthalmoplegia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

-0.67

CADD

Benign

1.3

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.036

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