rs2293284

Variant names:

• chr2-190060519-T-A
• rs2293284
• NM_005259.3:c.374-84A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005259.3(MSTN):​c.374-84A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,230,538 control chromosomes in the GnomAD database, including 3,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (1399 hom., cov: 32)
  • Exomes 𝑓: 0.033 (2073 hom.)
• Consequence: MSTN NM_005259.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.23
• Publications: 4 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-190060519-T-A is Benign according to our data. Variant chr2-190060519-T-A is described in ClinVar as Benign. ClinVar VariationId is 1258180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTN	NM_005259.3	MANE Select	c.374-84A>T		intron	N/A	NP_005250.1	O14793

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTN	ENST00000260950.5	TSL:1 MANE Select	c.374-84A>T		intron	N/A	ENSP00000260950.3	O14793
	C2orf88	ENST00000917871.1		c.-234-19435T>A		intron	N/A	ENSP00000587930.1
	C2orf88	ENST00000478197.1	TSL:4	n.220-18704T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14075 AN: 151892 Hom.: 1396 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0877

GnomAD4 exome AF: 0.0333 AC: 35956 AN: 1078528 Hom.: 2073 AF XY: 0.0320 AC XY: 17538 AN XY: 547290

African (AFR) AF: 0.262 AC: 6402 AN: 24436

American (AMR) AF: 0.113 AC: 3298 AN: 29112

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 1490 AN: 20700

East Asian (EAS) AF: 0.200 AC: 7299 AN: 36426

South Asian (SAS) AF: 0.0161 AC: 1071 AN: 66346

European-Finnish (FIN) AF: 0.00419 AC: 158 AN: 37692

Middle Eastern (MID) AF: 0.0631 AC: 209 AN: 3314

European-Non Finnish (NFE) AF: 0.0169 AC: 13758 AN: 813446

Other (OTH) AF: 0.0483 AC: 2271 AN: 47056

GnomAD4 genome AF: 0.0928 AC: 14108 AN: 152010 Hom.: 1399 Cov.: 32 AF XY: 0.0902 AC XY: 6703 AN XY: 74336

African (AFR) AF: 0.241 AC: 9974 AN: 41454

American (AMR) AF: 0.0954 AC: 1452 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 248 AN: 3464

East Asian (EAS) AF: 0.175 AC: 905 AN: 5178

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4820

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1222 AN: 67942

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0638 Hom.: 135

Bravo AF: 0.112

Asia WGS AF: 0.0720 AC: 248 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.030
DANN	Benign	0.27
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293284; hg19: chr2-190925245; COSMIC: COSV53621803;