rs15705

chr20-6779333-A-Cchr20-6779333-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001200.4(BMP2):c.*244A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 163,158 control chromosomes in the GnomAD database, including 4,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4607 hom., cov: 32)
  • Exomes 𝑓: 0.26 (386 hom.)
• Consequence: BMP2 NM_001200.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.35

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-6779333-A-C is Benign according to our data. Variant chr20-6779333-A-C is described in ClinVar as [Benign]. Clinvar id is 1169224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2	NM_001200.4	c.*244A>C		3_prime_UTR_variant	3/3	ENST00000378827.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2	ENST00000378827.5	c.*244A>C		3_prime_UTR_variant	3/3	1	NM_001200.4	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35844 AN: 151806 Hom.: 4602 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.259 AC: 2906 AN: 11234 Hom.: 386 Cov.: 0 AF XY: 0.257 AC XY: 1622 AN XY: 6308

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.236 AC: 35877 AN: 151924 Hom.: 4607 Cov.: 32 AF XY: 0.239 AC XY: 17726 AN XY: 74262

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.265

Alfa AF: 0.197 Hom.: 1189

Bravo AF: 0.235

Asia WGS AF: 0.402 AC: 1386 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	This variant is associated with the following publications: (PMID: 19492344, 20432245, 16497730, 27362534) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	16
Dann	Benign	0.90

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: rs15705; hg19: chr20-6759980; COSMIC: COSV66578883;