2-147905999-G-T

Variant names:

• chr2-147905999-G-T
• rs12987286
• NM_001616.5:c.528+6101G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001616.5(ACVR2A):​c.528+6101G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,936 control chromosomes in the GnomAD database, including 5,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5912 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 8 publications found

Genes affected

ACVR2A (HGNC:173): (activin A receptor type 2A) This gene encodes a receptor that mediates the functions of activins, which are members of the transforming growth factor-beta (TGF-beta) superfamily involved in diverse biological processes. The encoded protein is a transmembrane serine-threonine kinase receptor which mediates signaling by forming heterodimeric complexes with various combinations of type I and type II receptors and ligands in a cell-specific manner. The encoded type II receptor is primarily involved in ligand-binding and includes an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic serine-threonine kinase domain. This gene may be associated with susceptibility to preeclampsia, a pregnancy-related disease which can result in maternal and fetal morbidity and mortality. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001616.5. 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
	ACVR2A	NM_001616.5	MANE Select	c.528+6101G>T		intron	N/A	NP_001607.1	P27037-1
	ACVR2A	NM_001278579.2		c.528+6101G>T		intron	N/A	NP_001265508.1	P27037-1
	ACVR2A	NM_001278580.2		c.204+6101G>T		intron	N/A	NP_001265509.1	P27037-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.528+6101G>T		intron	N/A	ENSP00000241416.7	P27037-1
	ACVR2A	ENST00000404590.1	TSL:1	c.528+6101G>T		intron	N/A	ENSP00000384338.1	P27037-1
	ACVR2A	ENST00000943648.1		c.529-5538G>T		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39278 AN: 151816 Hom.: 5916 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39291 AN: 151936 Hom.: 5912 Cov.: 31 AF XY: 0.261 AC XY: 19410 AN XY: 74246

African (AFR) AF: 0.102 AC: 4241 AN: 41460

American (AMR) AF: 0.308 AC: 4697 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2370 AN: 5154

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3530 AN: 10560

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20988 AN: 67928

Other (OTH) AF: 0.293 AC: 617 AN: 2106

Alfa AF: 0.290 Hom.: 4411

Bravo AF: 0.255

Asia WGS AF: 0.308 AC: 1069 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.39
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12987286; hg19: chr2-148663568;