Genetic Variant NM_001106.4:c.20C>T (chr3-38454342-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001106.4(ACVR2B):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACVR2B
NM_001106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22698572).

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.20C>T	p.Ala7Val	missense	Exon 1 of 11	NP_001097.2	Q13705-1
	ACVR2B-AS1	NR_028389.1		n.318+161G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 11	ENSP00000340361.3	Q13705-1
ACVR2B	ENST00000922132.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 11	ENSP00000592191.1
ACVR2B	ENST00000465020.5	TSL:2	n.24C>T		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1145336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

553646

African (AFR)

AF:

0.00

AC:

AN:

23582

American (AMR)

AF:

0.00

AC:

AN:

13404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16992

East Asian (EAS)

AF:

0.00

AC:

AN:

26788

South Asian (SAS)

AF:

0.00

AC:

AN:

35536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3152

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

955458

Other (OTH)

AF:

0.00

AC:

AN:

45880

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Heterotaxy, visceral, 4, autosomal (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.55

PhyloP100

1.3

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.26

REVEL

Benign

0.21

Sift

Benign

0.52

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.34

MutPred

0.28

Loss of disorder (P = 0.0837)

MVP

0.52

MPC

0.76

ClinPred

0.12

GERP RS

2.7

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.096

gMVP

0.28

Mutation Taster

=93/7

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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