Variant 2-147920330-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001616.5(ACVR2A):c.1063G>A(p.Asp355Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,459,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ACVR2A
NM_001616.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

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]

ACVR2A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR2A	NM_001616.5 link	c.1063G>A	p.Asp355Asn	missense_variant	8/11	ENST00000241416.12	NP_001607.1	P27037-1
ACVR2A	NM_001278579.2 link	c.1063G>A	p.Asp355Asn	missense_variant	9/12		NP_001265508.1	P27037-1
ACVR2A	NM_001278580.2 link	c.739G>A	p.Asp247Asn	missense_variant	8/11		NP_001265509.1	P27037-2
ACVR2A	XM_047446292.1 link	c.739G>A	p.Asp247Asn	missense_variant	8/11		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACVR2A	ENST00000241416.12 link	c.1063G>A	p.Asp355Asn	missense_variant	8/11	1	NM_001616.5	ENSP00000241416.7	P27037-1
ACVR2A	ENST00000404590.1 link	c.1063G>A	p.Asp355Asn	missense_variant	9/12	1		ENSP00000384338.1	P27037-1
ACVR2A	ENST00000535787.5 link	c.739G>A	p.Asp247Asn	missense_variant	8/11	2		ENSP00000439988.1	P27037-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1459814

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000613

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.1063G>A (p.D355N) alteration is located in exon 8 (coding exon 8) of the ACVR2A gene. This alteration results from a G to A substitution at nucleotide position 1063, causing the aspartic acid (D) at amino acid position 355 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.7

L;.;L

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.27

Sift

Benign

0.059

T;T;T

Sift4G

Benign

0.072

T;T;T

Polyphen

0.98

D;.;D

Vest4

0.67

MutPred

0.28

Loss of phosphorylation at T356 (P = 0.1413);.;Loss of phosphorylation at T356 (P = 0.1413);

MVP

0.70

MPC

1.2

ClinPred

0.93

GERP RS

4.7

Varity_R

0.50

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over