20-6770387-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001200.4(BMP2):c.261A>G(p.Ser87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,632 control chromosomes in the GnomAD database, including 338,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38802 hom., cov: 32)
  • Exomes 𝑓: 0.64 (299243 hom.)
• Consequence: BMP2 NM_001200.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.31

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-6770387-A-G is Benign according to our data. Variant chr20-6770387-A-G is described in ClinVar as [Benign]. Clinvar id is 195136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2	NM_001200.4	c.261A>G	p.Ser87=	synonymous_variant	2/3	ENST00000378827.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2	ENST00000378827.5	c.261A>G	p.Ser87=	synonymous_variant	2/3	1	NM_001200.4	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107126 AN: 151936 Hom.: 38751 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.720

GnomAD3 exomes AF: 0.670 AC: 164002 AN: 244928 Hom.: 55757 AF XY: 0.662 AC XY: 88396 AN XY: 133542

Gnomad AFR exome AF: 0.863

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.809

Gnomad EAS exome AF: 0.830

Gnomad SAS exome AF: 0.606

Gnomad FIN exome AF: 0.581

Gnomad NFE exome AF: 0.629

Gnomad OTH exome AF: 0.680

GnomAD4 exome AF: 0.637 AC: 931010 AN: 1460578 Hom.: 299243 Cov.: 76 AF XY: 0.637 AC XY: 462704 AN XY: 726592

Gnomad4 AFR exome AF: 0.869

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.823

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.705 AC: 107232 AN: 152054 Hom.: 38802 Cov.: 32 AF XY: 0.702 AC XY: 52154 AN XY: 74302

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.722

Alfa AF: 0.651 Hom.: 40254

Bravo AF: 0.724

Asia WGS AF: 0.730 AC: 2535 AN: 3478

EpiCase AF: 0.634

EpiControl AF: 0.647

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 20, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.9
Dann	Benign	0.49

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: rs1049007; hg19: chr20-6751034; COSMIC: COSV66577791;