Genetic Variant MYOM2:p.Ser19Ser (chr8-2050823-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_003970.4(MYOM2):c.57C>T(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,613,556 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

MYOM2
NM_003970.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.17

Variant links:

Genes affected

MYOM2 (HGNC:7614): (myomesin 2) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008]

MYOM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-2050823-C-T is Benign according to our data. Variant chr8-2050823-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050181.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM2	NM_003970.4 link	c.57C>T	p.Ser19Ser	synonymous_variant	Exon 2 of 37	ENST00000262113.9	NP_003961.3	P54296

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9 link	c.57C>T	p.Ser19Ser	synonymous_variant	Exon 2 of 37	1	NM_003970.4	ENSP00000262113.4		P54296
MYOM2	ENST00000523438.1 link	c.-82+5655C>T		intron_variant	Intron 1 of 23	2		ENSP00000428396.1		E7EWH9

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000489

AC:

123

AN:

251446

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000207

AC:

302

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00589

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00165

AC:

251

AN:

152338

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

112

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00558

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000944

Hom.:

Bravo

AF:

0.00172

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYOM2-related disorder

Benign:1

Jul 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0060

DANN

Benign

0.63

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