dbSNP rs1364657: ACVR2A:c.55+15491T>C (chr2-147860698-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001616.5(ACVR2A):c.55+15491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,162 control chromosomes in the GnomAD database, including 57,925 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 0.86 ( 57925 hom., cov: 32)

Consequence

ACVR2A
NM_001616.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5 link	c.55+15491T>C	intron_variant	Intron 1 of 10	ENST00000241416.12	NP_001607.1	P27037-1
ACVR2A	NM_001278579.2 link	c.55+15491T>C	intron_variant	Intron 2 of 11		NP_001265508.1	P27037-1
ACVR2A	NM_001278580.2 link	c.-207+15992T>C	intron_variant	Intron 1 of 10		NP_001265509.1	P27037-2
ACVR2A	XM_047446292.1 link	c.-270+15992T>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 link	c.55+15491T>C		intron_variant	Intron 1 of 10	1	NM_001616.5	ENSP00000241416.7		P27037-1

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131109

AN:

152044

Hom.:

57890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.914

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.959

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.976

Gnomad FIN

AF:

0.980

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.937

Gnomad OTH

AF:

0.865

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

GnomAD4 genome

AF:

0.862

AC:

131202

AN:

152162

Hom.:

57925

Cov.:

AF XY:

0.868

AC XY:

64583

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.650

AC:

26924

AN:

41440

American (AMR)

AF:

0.915

AC:

13990

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.959

AC:

3328

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5171

AN:

5174

South Asian (SAS)

AF:

0.976

AC:

4711

AN:

4826

European-Finnish (FIN)

AF:

0.980

AC:

10406

AN:

10622

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.937

AC:

63749

AN:

68024

Other (OTH)

AF:

0.867

AC:

1832

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

797

1594

2390

3187

3984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.886

Hom.:

7905

Bravo

AF:

0.845

Asia WGS

AF:

0.960

AC:

3339

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.87

(source)

DANN

Benign

0.50

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over