Variant 2-190055744-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005259.3(MSTN):c.*1514C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,048 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.069 ( 868 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MSTN
NM_005259.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93

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=-0.9).

BP6

Variant 2-190055744-G-C is Benign according to our data. Variant chr2-190055744-G-C is described in ClinVar as [Benign]. Clinvar id is 333215.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MSTN	NM_005259.3 linkuse as main transcript	c.*1514C>G	3_prime_UTR_variant	3/3	ENST00000260950.5
C2orf88	XM_047446008.1 linkuse as main transcript	c.-517-24210G>C	intron_variant
C2orf88	XM_047446009.1 linkuse as main transcript	c.-517-24210G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MSTN	ENST00000260950.5 linkuse as main transcript	c.*1514C>G	3_prime_UTR_variant	3/3	1	NM_005259.3	P1
C2orf88	ENST00000478197.1 linkuse as main transcript	n.220-23479G>C	intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1 linkuse as main transcript	n.202-24210G>C	intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10522

AN:

151930

Hom.:

865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.000851

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0632

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.0694

AC:

10545

AN:

152048

Hom.:

868

Cov.:

AF XY:

0.0665

AC XY:

4945

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0640

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00727

Gnomad4 FIN

AF:

0.000851

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0626

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0787

Asia WGS

AF:

0.0140

AC:

AN:

3472

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

-0.90

CADD

Benign

2.5

DANN

Benign

0.64

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