rs35123420

Positions:

• chr20-6767952-G-C

Variant summary

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

The NM_001200.4(BMP2):​c.-931G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 395,260 control chromosomes in the GnomAD database, including 843 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 0.054 (309 hom., cov: 31)
  • Exomes 𝑓: 0.060 (534 hom.)
• Consequence: BMP2 NM_001200.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2	NM_001200.4	c.-931G>C		5_prime_UTR_variant	1/3	ENST00000378827.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2	ENST00000378827.5	c.-931G>C		5_prime_UTR_variant	1/3	1	NM_001200.4	P1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8162 AN: 151592 Hom.: 306 Cov.: 31

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0211

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0567

GnomAD4 exome AF: 0.0600 AC: 14621 AN: 243558 Hom.: 534 Cov.: 0 AF XY: 0.0602 AC XY: 7440 AN XY: 123614

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0347

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.0600

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.0610

GnomAD4 genome AF: 0.0539 AC: 8171 AN: 151702 Hom.: 309 Cov.: 31 AF XY: 0.0535 AC XY: 3965 AN XY: 74136

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0561

Alfa AF: 0.0643 Hom.: 62

Bravo AF: 0.0588

Asia WGS AF: 0.0130 AC: 45 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.83

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: rs35123420; hg19: chr20-6748599;