20-6779697-A-G

Variant names:

• chr20-6779697-A-G
• rs235769
• NM_001200.4:c.*608A>G

Variant summary

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

The NM_001200.4(BMP2):​c.*608A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,566 control chromosomes in the GnomAD database, including 41,951 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 0.73 (41892 hom., cov: 33)
  • Exomes 𝑓: 0.52 (59 hom.)
• Consequence: BMP2 NM_001200.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

BMP2 (HGNC:1069): (bone morphogenetic protein 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Duplication of a regulatory region downstream of this gene causes a form of brachydactyly characterized by a malformed index finger and second toe in human patients. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4	c.*608A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000378827.5	NP_001191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5	c.*608A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_001200.4	ENSP00000368104.3

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110679 AN: 152026 Hom.: 41831 Cov.: 33

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.521 AC: 220 AN: 422 Hom.: 59 Cov.: 0 AF XY: 0.516 AC XY: 133 AN XY: 258

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.728 AC: 110796 AN: 152144 Hom.: 41892 Cov.: 33 AF XY: 0.724 AC XY: 53845 AN XY: 74398

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.746

Alfa AF: 0.666 Hom.: 7148

Bravo AF: 0.750

Asia WGS AF: 0.737 AC: 2559 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.88

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: rs235769; hg19: chr20-6760344;