2-202376511-AGGCGGCGGCGGC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001204.7(BMPR2):c.-939_-928del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0029 (2 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43

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 -6 ACMG points.

• BP6: Variant 2-202376511-AGGCGGCGGCGGC-A is Benign according to our data. Variant chr2-202376511-AGGCGGCGGCGGC-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR2	NM_001204.7	c.-939_-928del		5_prime_UTR_variant	1/13	ENST00000374580.10
BMPR2	XM_011511687.2	c.-939_-928del		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.-939_-928del		5_prime_UTR_variant	1/13	1	NM_001204.7	P1

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 358 AN: 125752 Hom.: 2 Cov.: 16

Gnomad AFR AF: 0.00274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00771

Gnomad ASJ AF: 0.00157

Gnomad EAS AF: 0.000716

Gnomad SAS AF: 0.00441

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00386

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

GnomAD4 genome AF: 0.00285 AC: 359 AN: 125856 Hom.: 2 Cov.: 16 AF XY: 0.00284 AC XY: 171 AN XY: 60236

Gnomad4 AFR AF: 0.00273

Gnomad4 AMR AF: 0.00770

Gnomad4 ASJ AF: 0.00157

Gnomad4 EAS AF: 0.000719

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00381

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BMPR2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;