rs15705

Variant names:

• chr20-6779333-A-C
• rs15705
• NM_001200.4:c.*244A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-6779333-A-C
• chr20-6779333-A-T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 3.35
• Publications: 29 publications found

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]

BMP2 Gene-Disease associations (from GenCC):

• short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• brachydactyly type A2

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BMP2	NM_001200.4	c.*244A>C		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.*244A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001200.4	ENSP00000368104.3

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

African (AFR) AF: 0.243 AC: 71 AN: 292

American (AMR) AF: 0.228 AC: 94 AN: 412

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 162 AN: 398

East Asian (EAS) AF: 0.432 AC: 333 AN: 770

South Asian (SAS) AF: 0.205 AC: 23 AN: 112

European-Finnish (FIN) AF: 0.220 AC: 141 AN: 642

Middle Eastern (MID) AF: 0.360 AC: 18 AN: 50

European-Non Finnish (NFE) AF: 0.237 AC: 1881 AN: 7922

Other (OTH) AF: 0.288 AC: 183 AN: 636

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

African (AFR) AF: 0.212 AC: 8794 AN: 41480

American (AMR) AF: 0.206 AC: 3149 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2398 AN: 5174

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2305 AN: 10466

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15436 AN: 67944

Other (OTH) AF: 0.265 AC: 558 AN: 2106

Alfa AF: 0.227 Hom.: 7009

Bravo AF: 0.235

Asia WGS AF: 0.402 AC: 1386 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19492344, 20432245, 16497730, 27362534) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		3.3
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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