chr2-147917228-G-C

Variant names:

• chr2-147917228-G-C
• rs3764955
• NM_001616.5:c.673-55G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001616.5(ACVR2A):​c.673-55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,541,212 control chromosomes in the GnomAD database, including 72,097 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 (5956 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66141 hom.)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.673-55G>C		intron_variant	Intron 5 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.673-55G>C		intron_variant	Intron 6 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.349-55G>C		intron_variant	Intron 5 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.349-55G>C		intron_variant	Intron 5 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.673-55G>C		intron_variant	Intron 5 of 10	1	NM_001616.5	ENSP00000241416.7
ACVR2A	ENST00000404590.1	c.673-55G>C		intron_variant	Intron 6 of 11	1		ENSP00000384338.1
ACVR2A	ENST00000535787.5	c.349-55G>C		intron_variant	Intron 5 of 10	2		ENSP00000439988.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39455 AN: 151606 Hom.: 5960 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.304 AC: 422771 AN: 1389488 Hom.: 66141 AF XY: 0.304 AC XY: 208763 AN XY: 687032

African (AFR) AF: 0.0988 AC: 3037 AN: 30748

American (AMR) AF: 0.372 AC: 13509 AN: 36318

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8003 AN: 24422

East Asian (EAS) AF: 0.453 AC: 17013 AN: 37576

South Asian (SAS) AF: 0.296 AC: 22933 AN: 77490

European-Finnish (FIN) AF: 0.334 AC: 17484 AN: 52356

Middle Eastern (MID) AF: 0.405 AC: 2202 AN: 5438

European-Non Finnish (NFE) AF: 0.301 AC: 321364 AN: 1067758

Other (OTH) AF: 0.300 AC: 17226 AN: 57382

GnomAD4 genome AF: 0.260 AC: 39468 AN: 151724 Hom.: 5956 Cov.: 32 AF XY: 0.263 AC XY: 19487 AN XY: 74120

African (AFR) AF: 0.107 AC: 4444 AN: 41462

American (AMR) AF: 0.310 AC: 4706 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1093 AN: 3462

East Asian (EAS) AF: 0.463 AC: 2393 AN: 5172

South Asian (SAS) AF: 0.291 AC: 1399 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3530 AN: 10556

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20919 AN: 67752

Other (OTH) AF: 0.295 AC: 622 AN: 2108

Alfa AF: 0.283 Hom.: 820

Bravo AF: 0.257

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.66
PhyloP100		0.55
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: rs3764955; hg19: chr2-148674797; COSMIC: COSV54020226;