2-202376511-AGGCGGCGGC-A

Position:

• chr2-202376511-AGGCGGCGGC-A

Variant summary

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

The NM_001204.7(BMPR2):​c.-936_-928delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.0083 (11 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: 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-AGGCGGCGGC-A is Benign according to our data. Variant chr2-202376511-AGGCGGCGGC-A is described in ClinVar as [Benign]. Clinvar id is 3041823.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00834 (1049/125852) while in subpopulation AFR AF= 0.0148 (503/34012). AF 95% confidence interval is 0.0137. There are 11 homozygotes in gnomad4. There are 514 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1049 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-936_-928delGGCGGCGGC		5_prime_UTR_variant	1/13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-936_-928delGGCGGCGGC		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.-936_-928delGGCGGCGGC		5_prime_UTR_variant	1/13	1	NM_001204.7	ENSP00000363708.4

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1049 AN: 125748 Hom.: 11 Cov.: 16

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00138

Gnomad AMR AF: 0.00932

Gnomad ASJ AF: 0.00659

Gnomad EAS AF: 0.00334

Gnomad SAS AF: 0.00407

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00482

Gnomad OTH AF: 0.00643

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

GnomAD4 genome AF: 0.00834 AC: 1049 AN: 125852 Hom.: 11 Cov.: 16 AF XY: 0.00853 AC XY: 514 AN XY: 60230

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00659

Gnomad4 EAS AF: 0.00335

Gnomad4 SAS AF: 0.00408

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.00482

Gnomad4 OTH AF: 0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BMPR2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as 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;