2-202376511-A-AGGCGGC

Position:

• chr2-202376511-A-AGGCGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001204.7(BMPR2):​c.-933_-928dupGGCGGC 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 0.016 (28 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67

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 -10 ACMG points.

• BP6: Variant 2-202376511-A-AGGCGGC is Benign according to our data. Variant chr2-202376511-A-AGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1707255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0161 (2028/125840) while in subpopulation AFR AF= 0.0207 (705/34004). AF 95% confidence interval is 0.0195. There are 28 homozygotes in gnomad4. There are 949 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2028 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-933_-928dupGGCGGC		5_prime_UTR_variant	1/13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-933_-928dupGGCGGC		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.-933_-928dupGGCGGC		5_prime_UTR_variant	1/13	1	NM_001204.7	ENSP00000363708.4

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2022 AN: 125736 Hom.: 28 Cov.: 16

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00138

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00942

Gnomad EAS AF: 0.00334

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0147

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.00835

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

GnomAD4 genome AF: 0.0161 AC: 2028 AN: 125840 Hom.: 28 Cov.: 16 AF XY: 0.0158 AC XY: 949 AN XY: 60228

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00942

Gnomad4 EAS AF: 0.00335

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.00826

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2021

See Variant Classification Assertion Criteria. -

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;