rs3178250

Positions:

• chr20-6779554-T-C
• chr20-6779554-T-G

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.*465T>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 0.215 in 152,614 control chromosomes in the GnomAD database, including 3,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3897 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9 hom.)
• Consequence: BMP2 NM_001200.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.865

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=-0.6).
• BP6: Variant 20-6779554-T-C is Benign according to our data. Variant chr20-6779554-T-C is described in ClinVar as [Benign]. Clinvar id is 1169225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP2	NM_001200.4	c.*465T>C		3_prime_UTR_variant	3/3	ENST00000378827.5	NP_001191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5	c.*465T>C		3_prime_UTR_variant	3/3	1	NM_001200.4	ENSP00000368104.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32751 AN: 152070 Hom.: 3891 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.189 AC: 80 AN: 424 Hom.: 9 Cov.: 0 AF XY: 0.172 AC XY: 44 AN XY: 256

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.215 AC: 32790 AN: 152190 Hom.: 3897 Cov.: 32 AF XY: 0.217 AC XY: 16114 AN XY: 74416

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.241

Alfa AF: 0.215 Hom.: 4652

Bravo AF: 0.215

Asia WGS AF: 0.391 AC: 1356 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.8
DANN	Benign	0.85

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: rs3178250; hg19: chr20-6760201;