rs1709504660

Variant names:

• chr3-38454382-CTG-C
• rs1709504660
• NM_001106.4:c.52+9_52+10delTG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001106.4(ACVR2B):​c.52+9_52+10delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,254,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.640
• Publications: 0 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-AS1 (HGNC:44161): (ACVR2B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-38454382-CTG-C is Benign according to our data. Variant chr3-38454382-CTG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3054394.Status of the report is no_assertion_criteria_provided, 0 stars.

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.52+9_52+10delTG		intron	N/A	NP_001097.2	Q13705-1
	ACVR2B-AS1	NR_028389.1		n.318+119_318+120delCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.52+9_52+10delTG		intron	N/A	ENSP00000340361.3	Q13705-1
	ACVR2B	ENST00000922132.1		c.52+9_52+10delTG		intron	N/A	ENSP00000592191.1
	ACVR2B-AS1	ENST00000441531.1	TSL:2	n.318+119_318+120delCA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151958 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.07e-7 AC: 1 AN: 1102410 Hom.: 0 AF XY: 0.00000190 AC XY: 1 AN XY: 525598

African (AFR) AF: 0.00 AC: 0 AN: 22762

American (AMR) AF: 0.00 AC: 0 AN: 8484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14652

East Asian (EAS) AF: 0.00 AC: 0 AN: 26378

South Asian (SAS) AF: 0.00 AC: 0 AN: 27690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 932314

Other (OTH) AF: 0.0000226 AC: 1 AN: 44228

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151958 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74228

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ACVR2B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1709504660; hg19: chr3-38495873;