rs7270163

Variant names:

• chr20-6770669-A-G
• rs7270163
• NM_001200.4:c.346+197A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-6770669-A-G
• chr20-6770669-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001200.4(BMP2):​c.346+197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,198 control chromosomes in the GnomAD database, including 2,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2727 hom., cov: 33)
• Consequence: BMP2 NM_001200.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-6770669-A-G is Benign according to our data. Variant chr20-6770669-A-G is described in ClinVar as [Benign]. Clinvar id is 1222016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4	c.346+197A>G		intron_variant	Intron 2 of 2	ENST00000378827.5	NP_001191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5	c.346+197A>G		intron_variant	Intron 2 of 2	1	NM_001200.4	ENSP00000368104.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25576 AN: 152080 Hom.: 2727 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25594 AN: 152198 Hom.: 2727 Cov.: 33 AF XY: 0.165 AC XY: 12270 AN XY: 74430

African (AFR) AF: 0.292 AC: 12136 AN: 41496

American (AMR) AF: 0.168 AC: 2563 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3472

East Asian (EAS) AF: 0.192 AC: 993 AN: 5170

South Asian (SAS) AF: 0.112 AC: 540 AN: 4832

European-Finnish (FIN) AF: 0.0845 AC: 897 AN: 10616

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7448 AN: 68014

Other (OTH) AF: 0.161 AC: 338 AN: 2104

Alfa AF: 0.124 Hom.: 2151

Bravo AF: 0.181

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 2018

GeneDx

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	-0.74
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		0.24
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: rs7270163; hg19: chr20-6751316;