rs12477602

Positions:

• chr2-202473522-G-A
• chr2-202473522-G-T

Variant summary

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

The NM_001204.7(BMPR2):​c.418+5833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,138 control chromosomes in the GnomAD database, including 1,193 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 0.12 (1193 hom., cov: 33)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700

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=-0.93).
• 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.418+5833G>A		intron_variant		ENST00000374580.10
BMPR2	XM_011511687.2	c.418+5833G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.418+5833G>A		intron_variant		1	NM_001204.7	P1
BMPR2	ENST00000374574.2	c.418+5833G>A		intron_variant		2
BMPR2	ENST00000479069.1	n.326-1186G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18084 AN: 152020 Hom.: 1190 Cov.: 33

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.119 AC: 18101 AN: 152138 Hom.: 1193 Cov.: 33 AF XY: 0.120 AC XY: 8951 AN XY: 74354

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0889

Alfa AF: 0.0644 Hom.: 79

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.47

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: rs12477602; hg19: chr2-203338245;