2-147862177-T-C

Variant names:

• chr2-147862177-T-C
• rs1895694
• NM_001616.5:c.55+16970T>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.55+16970T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,968 control chromosomes in the GnomAD database, including 11,882 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 0.39 (11882 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 12 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.55+16970T>C		intron_variant	Intron 1 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.55+16970T>C		intron_variant	Intron 2 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.-207+17471T>C		intron_variant	Intron 1 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.-270+17471T>C		intron_variant	Intron 1 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.55+16970T>C		intron_variant	Intron 1 of 10	1	NM_001616.5	ENSP00000241416.7

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58817 AN: 151850 Hom.: 11869 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.387 AC: 58866 AN: 151968 Hom.: 11882 Cov.: 31 AF XY: 0.396 AC XY: 29417 AN XY: 74246

African (AFR) AF: 0.281 AC: 11644 AN: 41438

American (AMR) AF: 0.399 AC: 6097 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1945 AN: 5132

South Asian (SAS) AF: 0.503 AC: 2416 AN: 4804

European-Finnish (FIN) AF: 0.551 AC: 5811 AN: 10544

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28785 AN: 67988

Other (OTH) AF: 0.356 AC: 752 AN: 2110

Alfa AF: 0.403 Hom.: 53950

Bravo AF: 0.365

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.18
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: rs1895694; hg19: chr2-148619746; COSMIC: COSV54021256;