chr2-202390762-A-C

Position:

• chr2-202390762-A-C

Variant summary

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

The NM_001204.7(BMPR2):​c.76+13212A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,994 control chromosomes in the GnomAD database, including 4,230 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 0.20 (4230 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.76+13212A>C		intron_variant		ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.76+13212A>C		intron_variant			XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.76+13212A>C		intron_variant		1	NM_001204.7	ENSP00000363708	P1
BMPR2	ENST00000374574.2	c.76+13212A>C		intron_variant		2		ENSP00000363702

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31054 AN: 151876 Hom.: 4220 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.205 AC: 31093 AN: 151994 Hom.: 4230 Cov.: 31 AF XY: 0.204 AC XY: 15127 AN XY: 74282

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.202

Alfa AF: 0.138 Hom.: 1688

Bravo AF: 0.217

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.80

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: rs13426118; hg19: chr2-203255485;