rs2268757

Variant names:

• chr3-38464362-C-T
• rs2268757
• NM_001106.4:c.52+9988C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001106.4(ACVR2B):​c.52+9988C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,102 control chromosomes in the GnomAD database, including 15,948 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 0.42 (15948 hom., cov: 33)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 4, autosomal

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2B	NM_001106.4	c.52+9988C>T		intron_variant	Intron 1 of 10	ENST00000352511.5	NP_001097.2
ACVR2B	XM_005265583.4	c.115+4673C>T		intron_variant	Intron 1 of 10		XP_005265640.1
ACVR2B	XM_017007514.2	c.94+4694C>T		intron_variant	Intron 1 of 10		XP_016863003.1
ACVR2B	XM_017007515.3	c.70+9678C>T		intron_variant	Intron 1 of 10		XP_016863004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2B	ENST00000352511.5	c.52+9988C>T		intron_variant	Intron 1 of 10	1	NM_001106.4	ENSP00000340361.3
ACVR2B	ENST00000465020.5	n.56+9988C>T		intron_variant	Intron 1 of 9	2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64495 AN: 151984 Hom.: 15950 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.424 AC: 64496 AN: 152102 Hom.: 15948 Cov.: 33 AF XY: 0.421 AC XY: 31318 AN XY: 74322

African (AFR) AF: 0.180 AC: 7459 AN: 41498

American (AMR) AF: 0.384 AC: 5874 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1400 AN: 5180

South Asian (SAS) AF: 0.507 AC: 2440 AN: 4814

European-Finnish (FIN) AF: 0.527 AC: 5554 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38571 AN: 68004

Other (OTH) AF: 0.444 AC: 938 AN: 2114

Alfa AF: 0.465 Hom.: 3172

Bravo AF: 0.398

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.64
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2268757; hg19: chr3-38505853;