2-202376511-AGGC-A

Position:

• chr2-202376511-AGGC-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001204.7(BMPR2):​c.-930_-928delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0056 (4 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (699/125828) while in subpopulation AFR AF= 0.00888 (302/34000). AF 95% confidence interval is 0.00806. There are 4 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 699 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-930_-928delGGC		5_prime_UTR_variant	1/13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-930_-928delGGC		5_prime_UTR_variant	1/13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580	c.-930_-928delGGC		5_prime_UTR_variant	1/13	1	NM_001204.7	ENSP00000363708.4

Frequencies

GnomAD3 genomes AF: 0.00548 AC: 689 AN: 125724 Hom.: 3 Cov.: 16

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00314

Gnomad EAS AF: 0.00860

Gnomad SAS AF: 0.00238

Gnomad FIN AF: 0.000971

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.00257

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

GnomAD4 genome AF: 0.00556 AC: 699 AN: 125828 Hom.: 4 Cov.: 16 AF XY: 0.00556 AC XY: 335 AN XY: 60226

Gnomad4 AFR AF: 0.00888

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00314

Gnomad4 EAS AF: 0.00863

Gnomad4 SAS AF: 0.00238

Gnomad4 FIN AF: 0.000971

Gnomad4 NFE AF: 0.00513

Gnomad4 OTH AF: 0.00254

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pulmonary hypertension, primary, 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs375624016; hg19: chr2-203241234;