rs1085308076

Variant names:

• chr2-202520206-G-T
• rs1085307279
• NM_001204.7:c.967+5G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-202520206-G-T
• chr2-202520206-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001204.7(BMPR2):​c.967+5G>T variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMPR2 NM_001204.7 splice_region, intron
• Scores: Splicing: ADA: 0.9514
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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]

RPL13AP12 (HGNC:35673): (ribosomal protein L13a pseudogene 12)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-202520206-G-T is Pathogenic according to our data. Variant chr2-202520206-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 425851.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.967+5G>T		splice_region_variant, intron_variant	Intron 7 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.967+5G>T		splice_region_variant, intron_variant	Intron 7 of 12		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.967+5G>T		splice_region_variant, intron_variant	Intron 7 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.967+5G>T		splice_region_variant, intron_variant	Intron 7 of 11	2		ENSP00000363702.2
RPL13AP12	ENST00000435125.1	n.-195G>T		upstream_gene_variant		6

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

Submissions by phenotype

Pulmonary hypertension, primary, 1 Pathogenic:1

-

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Benign	0.97
PhyloP100		4.7
Mutation Taster		=2/98	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.56		Position offset: -5

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

Other links and lift over

dbSNP: rs1085307279; hg19: chr2-203384929;