Genetic Variant NM_001616.5:c.528+122A>T (chr2-147900020-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001616.5(ACVR2A):c.528+122A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACVR2A
NM_001616.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

10 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:

ENSG00000223911 (HGNC:):

ENSG00000223911 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ACVR2A	NM_001616.5 link	c.528+122A>T	intron_variant	Intron 4 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2 link	c.528+122A>T	intron_variant	Intron 5 of 11		NP_001265508.1
ACVR2A	NM_001278580.2 link	c.204+122A>T	intron_variant	Intron 4 of 10		NP_001265509.1
ACVR2A	XM_047446292.1 link	c.204+122A>T	intron_variant	Intron 4 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12 link	c.528+122A>T		intron_variant	Intron 4 of 10	1	NM_001616.5	ENSP00000241416.7

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

986398

Hom.:

AF XY:

0.00

AC XY:

AN XY:

493738

African (AFR)

AF:

0.00

AC:

AN:

21574

American (AMR)

AF:

0.00

AC:

AN:

22018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17450

East Asian (EAS)

AF:

0.00

AC:

AN:

33732

South Asian (SAS)

AF:

0.00

AC:

AN:

57450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4250

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

746282

Other (OTH)

AF:

0.00

AC:

AN:

43494

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67924

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

30631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.5

(source)

DANN

Benign

0.86

PhyloP100

1.0

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