2-202513709-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001204.7(BMPR2):​c.419-10T>C variant causes a splice polypyrimidine tract, 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: 32)

Consequence

BMPR2
NM_001204.7 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0005967
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.30
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-202513709-T-C is Pathogenic according to our data. Variant chr2-202513709-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 425783.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMPR2NM_001204.7 linkuse as main transcriptc.419-10T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000374580.10
BMPR2XM_011511687.2 linkuse as main transcriptc.419-10T>C splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMPR2ENST00000374580.10 linkuse as main transcriptc.419-10T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_001204.7 P1Q13873-1
BMPR2ENST00000374574.2 linkuse as main transcriptc.419-10T>C splice_polypyrimidine_tract_variant, intron_variant 2 Q13873-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Pulmonary hypertension, primary, 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyRare Disease Genomics Group, St George's University of London-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Benign
17
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00060
dbscSNV1_RF
Benign
0.076
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1085307231; hg19: chr2-203378432; API