2-202376545-G-GGCA

Variant summary

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

The NM_001204.7(BMPR2):c.-921_-919dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 140,572 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0038 (13 hom., cov: 26)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0750

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 2-202376545-G-GGCA is Benign according to our data. Variant chr2-202376545-G-GGCA is described in ClinVar as [Likely_benign]. Clinvar id is 333620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00378 (532/140572) while in subpopulation AMR AF= 0.0279 (372/13352). AF 95% confidence interval is 0.0255. There are 13 homozygotes in gnomad4. There are 298 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd at 527 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR2	NM_001204.7	c.-921_-919dup		5_prime_UTR_variant	1/13	ENST00000374580.10
BMPR2	XM_011511687.2	c.-921_-919dup		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.-921_-919dup		5_prime_UTR_variant	1/13	1	NM_001204.7	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 527 AN: 140458 Hom.: 13 Cov.: 26

Gnomad AFR AF: 0.000558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.000850

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000215

Gnomad OTH AF: 0.00458

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

GnomAD4 genome AF: 0.00378 AC: 532 AN: 140572 Hom.: 13 Cov.: 26 AF XY: 0.00440 AC XY: 298 AN XY: 67784

Gnomad4 AFR AF: 0.000557

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.00532

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.000850

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000215

Gnomad4 OTH AF: 0.00452

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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: rs568136148; hg19: chr2-203241268;