rs2303392

Positions:

• chr2-147922858-G-C
• chr2-147922858-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001616.5(ACVR2A):​c.1078-115G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,004,560 control chromosomes in the GnomAD database, including 56,067 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 0.33 (8530 hom., cov: 32)
  • Exomes 𝑓: 0.33 (47537 hom.)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.1078-115G>C		intron_variant		ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.1078-115G>C		intron_variant			NP_001265508.1
ACVR2A	NM_001278580.2	c.754-115G>C		intron_variant			NP_001265509.1
ACVR2A	XM_047446292.1	c.754-115G>C		intron_variant			XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.1078-115G>C		intron_variant		1	NM_001616.5	ENSP00000241416	P1
ACVR2A	ENST00000404590.1	c.1078-115G>C		intron_variant		1		ENSP00000384338	P1
ACVR2A	ENST00000535787.5	c.754-115G>C		intron_variant		2		ENSP00000439988

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50063 AN: 151824 Hom.: 8524 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.327 AC: 279169 AN: 852618 Hom.: 47537 AF XY: 0.327 AC XY: 143978 AN XY: 440900

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.330 AC: 50112 AN: 151942 Hom.: 8530 Cov.: 32 AF XY: 0.331 AC XY: 24588 AN XY: 74220

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.354

Alfa AF: 0.184 Hom.: 375

Bravo AF: 0.338

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs2303392; hg19: chr2-148680427;