2-202376511-A-AGGC

Variant names:

• chr2-202376511-A-AGGC
• rs375624016
• NM_001204.7:c.-930_-928dupGGC

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

BMPR2 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pulmonary hypertension, primary, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• heritable pulmonary arterial hypertension

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000273456 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	ENST00000374580.10	c.-930_-928dupGGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4
ENSG00000273456	ENST00000724884.1	n.154+277_154+279dupGCC		intron_variant	Intron 1 of 1
ENSG00000273456	ENST00000724885.1	n.106+119_106+121dupGCC		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.0653 AC: 2219 AN: 33986

American (AMR) AF: 0.0577 AC: 682 AN: 11816

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 285 AN: 3184

East Asian (EAS) AF: 0.0843 AC: 352 AN: 4174

South Asian (SAS) AF: 0.0986 AC: 290 AN: 2942

European-Finnish (FIN) AF: 0.0466 AC: 384 AN: 8244

Middle Eastern (MID) AF: 0.109 AC: 28 AN: 258

European-Non Finnish (NFE) AF: 0.0793 AC: 4669 AN: 58896

Other (OTH) AF: 0.0561 AC: 88 AN: 1570

Alfa AF: 0.0199 Hom.: 30

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Nov 20, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pulmonary hypertension, primary, 1 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375624016; hg19: chr2-203241234;