2-202513893-C-T

Position:

• chr2-202513893-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204.7(BMPR2):​c.529+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,290,226 control chromosomes in the GnomAD database, including 11,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1185 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10236 hom.)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-202513893-C-T is Benign according to our data. Variant chr2-202513893-C-T is described in ClinVar as [Benign]. Clinvar id is 1281801.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/exons	MANE	UniProt
BMPR2	NM_001204.7	c.529+64C>T		intron_variant		ENST00000374580.10
BMPR2	XM_011511687.2	c.529+64C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.529+64C>T		intron_variant		1	NM_001204.7	P1
BMPR2	ENST00000374574.2	c.529+64C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18050 AN: 151674 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0693

Gnomad EAS AF: 0.00387

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.129 AC: 146636 AN: 1138432 Hom.: 10236 AF XY: 0.129 AC XY: 74512 AN XY: 579616

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0632

Gnomad4 EAS exome AF: 0.00222

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.119 AC: 18067 AN: 151794 Hom.: 1185 Cov.: 32 AF XY: 0.120 AC XY: 8937 AN XY: 74168

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0693

Gnomad4 EAS AF: 0.00407

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.126 Hom.: 195

Bravo AF: 0.112

Asia WGS AF: 0.0450 AC: 157 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs7575056; hg19: chr2-203378616;