Genetic Variant ACVR2B:p.Ala3Ala (chr3-38454331-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001106.4(ACVR2B):c.9G>T(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,146,866 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. Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

ACVR2B
NM_001106.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

0 publications found

Variant links:

Genes affected

ACVR2B (HGNC:174): (activin A receptor type 2B) Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively active kinases. This gene encodes activin A type IIB receptor, which displays a 3- to 4-fold higher affinity for the ligand than activin A type II receptor. [provided by RefSeq, Jul 2008]

ACVR2B links:

ACVR2B-AS1 (HGNC:44161): (ACVR2B antisense RNA 1)

ACVR2B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=0.212 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001106.4. 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
	ACVR2B	NM_001106.4	MANE Select	c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 11	NP_001097.2	Q13705-1
	ACVR2B-AS1	NR_028389.1		n.318+172C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 11	ENSP00000340361.3	Q13705-1
ACVR2B	ENST00000922132.1		c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 11	ENSP00000592191.1
ACVR2B	ENST00000465020.5	TSL:2	n.13G>T		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000262

AC:

AN:

1146866

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

554548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23696

American (AMR)

AF:

0.00

AC:

AN:

14300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17148

East Asian (EAS)

AF:

0.00

AC:

AN:

26610

South Asian (SAS)

AF:

0.00

AC:

AN:

36006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3164

European-Non Finnish (NFE)

AF:

0.00000314

AC:

AN:

955482

Other (OTH)

AF:

0.00

AC:

AN:

45918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.21

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over