rs387906389

Variant names:

• chr12-51986839-TGATGA-T
• rs387906389
• NM_004302.5:c.1159_1163delGATGA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004302.5(ACVR1B):​c.1159_1163delGATGA​(p.Asp387AsnfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACVR1B NM_004302.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

ACVR1B (HGNC:172): (activin A receptor type 1B) This gene encodes an activin A type IB receptor. 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 and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

ACVR1B Gene-Disease associations (from GenCC):

• malignant pancreatic neoplasm

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-51986839-TGATGA-T is Pathogenic according to our data. Variant chr12-51986839-TGATGA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 8227.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004302.5. 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
	ACVR1B	NM_004302.5	MANE Select	c.1159_1163delGATGA	p.Asp387AsnfsTer3	frameshift	Exon 7 of 9	NP_004293.1	P36896-1
	ACVR1B	NM_020328.4		c.1282_1286delGATGA	p.Asp428AsnfsTer3	frameshift	Exon 8 of 10	NP_064733.3
	ACVR1B	NM_001412774.1		c.1279_1283delGATGA	p.Asp427AsnfsTer3	frameshift	Exon 8 of 10	NP_001399703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.1159_1163delGATGA	p.Asp387AsnfsTer3	frameshift	Exon 7 of 9	ENSP00000257963.4	P36896-1
	ACVR1B	ENST00000541224.5	TSL:2	c.1282_1286delGATGA	p.Asp428AsnfsTer3	frameshift	Exon 8 of 10	ENSP00000442656.1	P36896-4
	ACVR1B	ENST00000900350.1		c.1279_1283delGATGA	p.Asp427AsnfsTer3	frameshift	Exon 8 of 10	ENSP00000570409.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Carcinoma of pancreas (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=2/198	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs387906389; hg19: chr12-52380623; COSMIC: COSV57781273;