rs143555593

Positions:

• chr17-10539165-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0100

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]

MYHAS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 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.
• BS2: High Homozygotes in GnomAdExome4 at 8 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH2	NM_017534.6	c.1416+40G>C		intron_variant		ENST00000245503.10	NP_060004.3
MYHAS	NR_125367.1	n.168-28372C>G		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.1416+40G>C		intron_variant			NP_001093582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.1416+40G>C		intron_variant		1	NM_017534.6	ENSP00000245503	P1
MYH2	ENST00000532183.6	c.1416+40G>C		intron_variant		1		ENSP00000433944
MYH2	ENST00000622564.4	c.1416+40G>C		intron_variant		1		ENSP00000482463
MYH2	ENST00000397183.6	c.1416+40G>C		intron_variant		5		ENSP00000380367	P1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 153 AN: 152086 Hom.: 1 Cov.: 32

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.: 3 AF XY: 0.00220 AC XY: 299 AN XY: 135732

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.: 8 Cov.: 32 AF XY: 0.000541 AC XY: 393 AN XY: 727028

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.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74398

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.: 0

Bravo AF: 0.00156

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs143555593; hg19: chr17-10442482;