NM_001200.4:c.*608A>G

Variant names:

• chr20-6779697-A-G
• rs235769
• NM_001200.4:c.*608A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001200.4(BMP2):​c.*608A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,566 control chromosomes in the GnomAD database, including 41,951 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (41892 hom., cov: 33)
  • Exomes 𝑓: 0.52 (59 hom.)
• Consequence: BMP2 NM_001200.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2	NM_001200.4	MANE Select	c.*608A>G		3_prime_UTR	Exon 3 of 3	NP_001191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2	ENST00000378827.5	TSL:1 MANE Select	c.*608A>G		3_prime_UTR	Exon 3 of 3	ENSP00000368104.3
	BMP2	ENST00000936876.1		c.*608A>G		3_prime_UTR	Exon 2 of 2	ENSP00000606935.1
	BMP2	ENST00000953442.1		c.*608A>G		3_prime_UTR	Exon 3 of 3	ENSP00000623501.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110679 AN: 152026 Hom.: 41831 Cov.: 33

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.521 AC: 220 AN: 422 Hom.: 59 Cov.: 0 AF XY: 0.516 AC XY: 133 AN XY: 258

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: 0.522 AC: 217 AN: 416

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.728 AC: 110796 AN: 152144 Hom.: 41892 Cov.: 33 AF XY: 0.724 AC XY: 53845 AN XY: 74398

African (AFR) AF: 0.932 AC: 38696 AN: 41530

American (AMR) AF: 0.724 AC: 11065 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4224 AN: 5172

South Asian (SAS) AF: 0.611 AC: 2950 AN: 4830

European-Finnish (FIN) AF: 0.574 AC: 6061 AN: 10554

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42562 AN: 67982

Other (OTH) AF: 0.746 AC: 1576 AN: 2114

Alfa AF: 0.671 Hom.: 7455

Bravo AF: 0.750

Asia WGS AF: 0.737 AC: 2559 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		1.7
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: rs235769; hg19: chr20-6760344;