rs3178250

Variant names:

• chr20-6779554-T-C
• rs3178250
• NM_001200.4:c.*465T>C

Your query was ambiguous. Multiple possible variants found:

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

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.*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
• Publications: 48 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=-0.6).
• BP6: Variant 20-6779554-T-C is Benign according to our data. Variant chr20-6779554-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001200.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2	NM_001200.4	MANE Select	c.*465T>C		3_prime_UTR	Exon 3 of 3	NP_001191.1	P12643

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2	ENST00000378827.5	TSL:1 MANE Select	c.*465T>C		3_prime_UTR	Exon 3 of 3	ENSP00000368104.3	P12643
	BMP2	ENST00000936876.1		c.*465T>C		3_prime_UTR	Exon 2 of 2	ENSP00000606935.1
	BMP2	ENST00000953442.1		c.*465T>C		3_prime_UTR	Exon 3 of 3	ENSP00000623501.1

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

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: 0.187 AC: 78 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.193 AC: 8003 AN: 41520

American (AMR) AF: 0.190 AC: 2911 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2398 AN: 5164

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1943 AN: 10604

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14012 AN: 67990

Other (OTH) AF: 0.241 AC: 510 AN: 2116

Alfa AF: 0.215 Hom.: 7507

Bravo AF: 0.215

Asia WGS AF: 0.391 AC: 1356 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.8
DANN	Benign	0.85
PhyloP100		0.86
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: rs3178250; hg19: chr20-6760201;