rs1199496

Positions:

• chr2-202544013-T-A
• chr2-202544013-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204.7(BMPR2):​c.1413+1566T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,668 control chromosomes in the GnomAD database, including 6,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6007 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR2	NM_001204.7	c.1413+1566T>A		intron_variant		ENST00000374580.10
BMPR2	XM_011511687.2	c.1413+1566T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.1413+1566T>A		intron_variant		1	NM_001204.7	P1
BMPR2	ENST00000374574.2	c.1413+1566T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42856 AN: 151552 Hom.: 6007 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.283 AC: 42861 AN: 151668 Hom.: 6007 Cov.: 31 AF XY: 0.283 AC XY: 20936 AN XY: 74080

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.272

Alfa AF: 0.160 Hom.: 276

Bravo AF: 0.284

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.98
DANN	Benign	0.84

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: rs1199496; hg19: chr2-203408736;