rs13037675

Variant names:

• chr20-6779059-C-T
• rs13037675
• NM_001200.4:c.1161C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001200.4(BMP2):​c.1161C>T​(p.Asp387Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,610,308 control chromosomes in the GnomAD database, including 4,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (373 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3818 hom.)
• Consequence: BMP2 NM_001200.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.20
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 20-6779059-C-T is Benign according to our data. Variant chr20-6779059-C-T is described in ClinVar as Benign. ClinVar VariationId is 257620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.12 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.1161C>T	p.Asp387Asp	synonymous	Exon 3 of 3	NP_001191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2	ENST00000378827.5	TSL:1 MANE Select	c.1161C>T	p.Asp387Asp	synonymous	Exon 3 of 3	ENSP00000368104.3
	BMP2	ENST00000936876.1		c.1161C>T	p.Asp387Asp	synonymous	Exon 2 of 2	ENSP00000606935.1
	BMP2	ENST00000953442.1		c.1161C>T	p.Asp387Asp	synonymous	Exon 3 of 3	ENSP00000623501.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9624 AN: 151264 Hom.: 369 Cov.: 31

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0675

GnomAD2 exomes AF: 0.0695 AC: 17228 AN: 247714 AF XY: 0.0637

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.0303

Gnomad EAS exome AF: 0.000762

Gnomad FIN exome AF: 0.0592

Gnomad NFE exome AF: 0.0687

Gnomad OTH exome AF: 0.0703

GnomAD4 exome AF: 0.0670 AC: 97699 AN: 1458938 Hom.: 3818 Cov.: 35 AF XY: 0.0652 AC XY: 47295 AN XY: 725832

African (AFR) AF: 0.0467 AC: 1562 AN: 33454

American (AMR) AF: 0.170 AC: 7589 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 873 AN: 26100

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39698

South Asian (SAS) AF: 0.0251 AC: 2168 AN: 86206

European-Finnish (FIN) AF: 0.0608 AC: 3150 AN: 51780

Middle Eastern (MID) AF: 0.0385 AC: 222 AN: 5764

European-Non Finnish (NFE) AF: 0.0705 AC: 78309 AN: 1110884

Other (OTH) AF: 0.0632 AC: 3814 AN: 60350

GnomAD4 genome AF: 0.0637 AC: 9640 AN: 151370 Hom.: 373 Cov.: 31 AF XY: 0.0632 AC XY: 4669 AN XY: 73918

African (AFR) AF: 0.0494 AC: 2038 AN: 41284

American (AMR) AF: 0.124 AC: 1887 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.0256 AC: 122 AN: 4774

European-Finnish (FIN) AF: 0.0546 AC: 565 AN: 10350

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4748 AN: 67850

Other (OTH) AF: 0.0669 AC: 140 AN: 2092

Alfa AF: 0.0599 Hom.: 207

Bravo AF: 0.0699

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.0651

EpiControl AF: 0.0637

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.9
DANN	Benign	0.64
PhyloP100		2.2
Mutation Taster		=99/1	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: rs13037675; hg19: chr20-6759706;