chr2-202376511-AGGCGGCGGCGGCGGC-A

Variant names:

• chr2-202376511-AGGCGGCGGCGGCGGC-A
• rs375624016
• NM_001204.7:c.-942_-928delGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001204.7(BMPR2):​c.-942_-928delGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000095 (0 hom., cov: 16)
• Consequence: BMPR2 NM_001204.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 3 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

ENSG00000273456 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	NM_001204.7	MANE Select	c.-942_-928delGGCGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 13	NP_001195.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	ENST00000374580.10	TSL:1 MANE Select	c.-942_-928delGGCGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 13	ENSP00000363708.4	Q13873-1
	ENSG00000273456	ENST00000724884.1		n.154+265_154+279delGCCGCCGCCGCCGCC		intron	N/A
	ENSG00000273456	ENST00000724885.1		n.106+107_106+121delGCCGCCGCCGCCGCC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000954 AC: 12 AN: 125764 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000314

Gnomad EAS AF: 0.000716

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000509

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000953 AC: 12 AN: 125868 Hom.: 0 Cov.: 16 AF XY: 0.0000830 AC XY: 5 AN XY: 60244

African (AFR) AF: 0.000147 AC: 5 AN: 34014

American (AMR) AF: 0.00 AC: 0 AN: 11822

Ashkenazi Jewish (ASJ) AF: 0.000314 AC: 1 AN: 3186

East Asian (EAS) AF: 0.000719 AC: 3 AN: 4174

South Asian (SAS) AF: 0.00 AC: 0 AN: 2942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000509 AC: 3 AN: 58922

Other (OTH) AF: 0.00 AC: 0 AN: 1574

Alfa AF: 0.00 Hom.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

Other links and lift over

dbSNP: rs375624016; hg19: chr2-203241234;