ENST00000374580:c.-939_-928delGGCGGCGGCGGC

Variant names:

• chr2-202376511-AGGCGGCGGCGGC-A
• rs375624016
• NM_001204.7:c.-939_-928delGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000374580(BMPR2):​c.-939_-928delGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.0029 (2 hom., cov: 16)
• Consequence: BMPR2 ENST00000374580 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided 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 Benign. Variant got -9 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 no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00285 (359/125856) while in subpopulation AMR AF= 0.0077 (91/11818). AF 95% confidence interval is 0.00642. There are 2 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-939_-928delGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-939_-928delGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580	c.-939_-928delGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4

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: no assertion criteria provided

Submissions by phenotype

BMPR2-related disorder Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;