2-202376511-A-AGGCGGCGGC

Variant names:

• chr2-202376511-A-AGGCGGCGGC
• rs375624016
• NM_001204.7:c.-936_-928dupGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001204.7(BMPR2):​c.-936_-928dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (457 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 2-202376511-A-AGGCGGCGGC is Benign according to our data. Variant chr2-202376511-A-AGGCGGCGGC is described in ClinVar as [Benign]. Clinvar id is 1238911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.-936_-928dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.-936_-928dupGGCGGCGGC		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.-936_-928dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4
ENSG00000273456	ENST00000724884.1	n.154+271_154+279dupGCCGCCGCC		intron_variant	Intron 1 of 1
ENSG00000273456	ENST00000724885.1	n.106+113_106+121dupGCCGCCGCC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 9247 AN: 125682 Hom.: 456 Cov.: 16

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0468

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.00382

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0551

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0736 AC: 9256 AN: 125786 Hom.: 457 Cov.: 16 AF XY: 0.0710 AC XY: 4274 AN XY: 60200

African (AFR) AF: 0.0428 AC: 1457 AN: 34004

American (AMR) AF: 0.0912 AC: 1077 AN: 11808

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 236 AN: 3186

East Asian (EAS) AF: 0.00383 AC: 16 AN: 4174

South Asian (SAS) AF: 0.0595 AC: 175 AN: 2942

European-Finnish (FIN) AF: 0.0746 AC: 614 AN: 8232

Middle Eastern (MID) AF: 0.0538 AC: 14 AN: 260

European-Non Finnish (NFE) AF: 0.0944 AC: 5557 AN: 58880

Other (OTH) AF: 0.0483 AC: 76 AN: 1574

Alfa AF: 0.0259 Hom.: 30

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;