2-202376511-A-AGGC

Position:

• chr2-202376511-A-AGGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001204.7(BMPR2):​c.-930_-928dupGGC 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 0.072 (387 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 2-202376511-A-AGGC is Benign according to our data. Variant chr2-202376511-A-AGGC is described in ClinVar as [Likely_benign]. Clinvar id is 333617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-930_-928dupGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-930_-928dupGGC		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.-930_-928dupGGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 9008 AN: 125692 Hom.: 388 Cov.: 16

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0895

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0567

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

GnomAD4 genome AF: 0.0717 AC: 9017 AN: 125796 Hom.: 387 Cov.: 16 AF XY: 0.0682 AC XY: 4106 AN XY: 60210

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.0577

Gnomad4 ASJ AF: 0.0895

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.0561

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 20, 2020

- -

Pulmonary hypertension, primary, 1 Benign:1

Likely benign, 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;