rs170986

Variant names:

• chr20-6779784-C-A
• rs170986
• NM_001200.4:c.*695C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001200.4(BMP2):​c.*695C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,412 control chromosomes in the GnomAD database, including 3,621 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 0.20 (3618 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: BMP2 NM_001200.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4	c.*695C>A		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.*695C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001200.4	ENSP00000368104.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30508 AN: 151984 Hom.: 3616 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.116 AC: 36 AN: 310 Hom.: 3 Cov.: 0 AF XY: 0.126 AC XY: 23 AN XY: 182

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.118 AC: 36 AN: 306

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.201 AC: 30532 AN: 152102 Hom.: 3618 Cov.: 32 AF XY: 0.194 AC XY: 14418 AN XY: 74366

African (AFR) AF: 0.304 AC: 12597 AN: 41470

American (AMR) AF: 0.256 AC: 3916 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5184

South Asian (SAS) AF: 0.0713 AC: 344 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1140 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11551 AN: 67984

Other (OTH) AF: 0.190 AC: 401 AN: 2112

Alfa AF: 0.175 Hom.: 4025

Bravo AF: 0.219

Asia WGS AF: 0.0690 AC: 241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.53
PhyloP100		0.047
Mutation Taster		=100/0	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: rs170986; hg19: chr20-6760431;