rs1085307329

chr2-202532735-A-Gchr2-202532735-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001204.7(BMPR2):c.1276+3A>G variant causes a splice donor region, intron 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BMPR2 NM_001204.7 splice_donor_region, intron
• Scores: Splicing: ADA: 0.8901
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.411

Genes affected

BMPR2 (HGNC:1078): (bone morphogenetic protein receptor type 2) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-202532735-A-G is Pathogenic according to our data. Variant chr2-202532735-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 425912.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR2	NM_001204.7	c.1276+3A>G		splice_donor_region_variant, intron_variant		ENST00000374580.10
BMPR2	XM_011511687.2	c.1276+3A>G		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.1276+3A>G		splice_donor_region_variant, intron_variant		1	NM_001204.7	P1
BMPR2	ENST00000374574.2	c.1276+3A>G		splice_donor_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary hypertension, primary, 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

Rare Disease Genomics Group, St George's University of London

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	9.3
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Pathogenic	0.73
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.59		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1085307329; hg19: chr2-203397458;