2-190056765-C-T

Position:

chr2-190056765-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005259.3(MSTN):c.*493G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 164,046 control chromosomes in the GnomAD database, including 855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.069 ( 847 hom., cov: 32)

Exomes 𝑓: 0.014 ( 8 hom. )

Consequence

MSTN
NM_005259.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

MSTN (HGNC:4223): (myostatin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein negatively regulates skeletal muscle cell proliferation and differentiation. Mutations in this gene are associated with increased skeletal muscle mass in humans and other mammals. [provided by RefSeq, Jul 2016]

MSTN links:

C2orf88 (HGNC:28191): (chromosome 2 open reading frame 88) Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2orf88 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-190056765-C-T is Benign according to our data. Variant chr2-190056765-C-T is described in ClinVar as [Benign]. Clinvar id is 333226.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
MSTN	NM_005259.3 linkuse as main transcript	c.*493G>A	3_prime_UTR_variant	3/3	ENST00000260950.5	NP_005250.1
C2orf88	XM_047446008.1 linkuse as main transcript	c.-517-23189C>T	intron_variant			XP_047301964.1
C2orf88	XM_047446009.1 linkuse as main transcript	c.-517-23189C>T	intron_variant			XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
MSTN	ENST00000260950.5 linkuse as main transcript	c.*493G>A	3_prime_UTR_variant	3/3	1	NM_005259.3	ENSP00000260950	P1
C2orf88	ENST00000478197.1 linkuse as main transcript	n.220-22458C>T	intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1 linkuse as main transcript	n.202-23189C>T	intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0685

AC:

10410

AN:

151934

Hom.:

844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0618

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0631

GnomAD4 exome

AF:

0.0143

AC:

172

AN:

11994

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

100

AN XY:

6294

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.0262

Gnomad4 ASJ exome

AF:

0.0882

Gnomad4 EAS exome

AF:

0.00155

Gnomad4 SAS exome

AF:

0.00569

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0686

AC:

10433

AN:

152052

Hom.:

847

Cov.:

AF XY:

0.0660

AC XY:

4907

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.0458

Gnomad4 ASJ

AF:

0.0618

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0259

Hom.:

234

Bravo

AF:

0.0780

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myostatin-related muscle hypertrophy

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.67

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