rs7600694

Variant names:

• chr2-202565944-G-A
• rs7600694
• NM_001204.7:c.*5998G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-202565944-G-A
• chr2-202565944-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204.7(BMPR2):​c.*5998G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,034 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1187 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: BMPR2 NM_001204.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.417
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-202565944-G-A is Benign according to our data. Variant chr2-202565944-G-A is described in ClinVar as Benign. ClinVar VariationId is 333717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.*5998G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.*5998G>A		3_prime_UTR_variant	Exon 13 of 13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.*5998G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.*6242G>A		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18284 AN: 151916 Hom.: 1183 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0690

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0947

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.120 AC: 18311 AN: 152034 Hom.: 1187 Cov.: 32 AF XY: 0.122 AC XY: 9062 AN XY: 74306

African (AFR) AF: 0.0957 AC: 3972 AN: 41504

American (AMR) AF: 0.136 AC: 2071 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 239 AN: 3466

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5188

South Asian (SAS) AF: 0.114 AC: 550 AN: 4822

European-Finnish (FIN) AF: 0.189 AC: 1992 AN: 10544

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9178 AN: 67926

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.112 Hom.: 1010

Bravo AF: 0.113

Asia WGS AF: 0.0460 AC: 161 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pulmonary hypertension, primary, 1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.42
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7600694; hg19: chr2-203430667;