2-147857961-C-T

Variant names:

• chr2-147857961-C-T
• rs13034494
• NM_001616.5:c.55+12754C>T

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+12754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,836 control chromosomes in the GnomAD database, including 6,467 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 0.28 (6467 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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.55+12754C>T		intron	N/A	NP_001607.1
	ACVR2A	NM_001278579.2		c.55+12754C>T		intron	N/A	NP_001265508.1
	ACVR2A	NM_001278580.2		c.-207+13255C>T		intron	N/A	NP_001265509.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.55+12754C>T		intron	N/A	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.55+12754C>T		intron	N/A	ENSP00000384338.1
	ACVR2A	ENST00000943648.1		c.55+12754C>T		intron	N/A	ENSP00000613707.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42754 AN: 151718 Hom.: 6466 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.282 AC: 42796 AN: 151836 Hom.: 6467 Cov.: 31 AF XY: 0.283 AC XY: 21029 AN XY: 74192

African (AFR) AF: 0.181 AC: 7494 AN: 41398

American (AMR) AF: 0.319 AC: 4854 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2374 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4814

European-Finnish (FIN) AF: 0.336 AC: 3539 AN: 10544

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21025 AN: 67914

Other (OTH) AF: 0.310 AC: 652 AN: 2102

Alfa AF: 0.293 Hom.: 866

Bravo AF: 0.281

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.54
PhyloP100		0.30
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: rs13034494; hg19: chr2-148615530;