chr2-147865408-T-G

Variant names:

• chr2-147865408-T-G
• rs2113794
• NM_001616.5:c.55+20201T>G

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+20201T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,968 control chromosomes in the GnomAD database, including 11,886 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 (11886 hom., cov: 32)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 6 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=-0.83).
• 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+20201T>G		intron_variant	Intron 1 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.55+20201T>G		intron_variant	Intron 2 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.-207+20702T>G		intron_variant	Intron 1 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.-270+20702T>G		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+20201T>G		intron_variant	Intron 1 of 10	1	NM_001616.5	ENSP00000241416.7

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58847 AN: 151850 Hom.: 11873 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.388 AC: 58896 AN: 151968 Hom.: 11886 Cov.: 32 AF XY: 0.396 AC XY: 29444 AN XY: 74280

African (AFR) AF: 0.281 AC: 11662 AN: 41448

American (AMR) AF: 0.399 AC: 6093 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 982 AN: 3462

East Asian (EAS) AF: 0.380 AC: 1961 AN: 5164

South Asian (SAS) AF: 0.503 AC: 2425 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5823 AN: 10548

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

European-Non Finnish (NFE) AF: 0.423 AC: 28768 AN: 67936

Other (OTH) AF: 0.358 AC: 753 AN: 2104

Alfa AF: 0.408 Hom.: 1709

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	-0.83
CADD	Benign	0.64
DANN	Benign	0.49
PhyloP100		-1.1
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: rs2113794; hg19: chr2-148622977;