20-6767952-G-C

Variant names:

• chr20-6767952-G-C
• rs35123420
• NM_001200.4:c.-931G>C

Variant summary

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

The NM_001200.4(BMP2):​c.-931G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 395,260 control chromosomes in the GnomAD database, including 843 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 0.054 (309 hom., cov: 31)
  • Exomes 𝑓: 0.060 (534 hom.)
• Consequence: BMP2 NM_001200.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 3 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

ENSG00000302641 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 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.-931G>C		5_prime_UTR	Exon 1 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.-931G>C		5_prime_UTR	Exon 1 of 3	ENSP00000368104.3
	ENSG00000302641	ENST00000788333.1		n.71+647C>G		intron	N/A
	ENSG00000302641	ENST00000788334.1		n.88+345C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8162 AN: 151592 Hom.: 306 Cov.: 31

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0211

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0567

GnomAD4 exome AF: 0.0600 AC: 14621 AN: 243558 Hom.: 534 Cov.: 0 AF XY: 0.0602 AC XY: 7440 AN XY: 123614

African (AFR) AF: 0.0123 AC: 86 AN: 6996

American (AMR) AF: 0.135 AC: 990 AN: 7322

Ashkenazi Jewish (ASJ) AF: 0.0347 AC: 315 AN: 9074

East Asian (EAS) AF: 0.000132 AC: 3 AN: 22744

South Asian (SAS) AF: 0.0304 AC: 90 AN: 2964

European-Finnish (FIN) AF: 0.0600 AC: 1247 AN: 20790

Middle Eastern (MID) AF: 0.0338 AC: 43 AN: 1274

European-Non Finnish (NFE) AF: 0.0695 AC: 10861 AN: 156236

Other (OTH) AF: 0.0610 AC: 986 AN: 16158

GnomAD4 genome AF: 0.0539 AC: 8171 AN: 151702 Hom.: 309 Cov.: 31 AF XY: 0.0535 AC XY: 3965 AN XY: 74136

African (AFR) AF: 0.0152 AC: 630 AN: 41490

American (AMR) AF: 0.113 AC: 1729 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.0262 AC: 126 AN: 4818

European-Finnish (FIN) AF: 0.0546 AC: 572 AN: 10482

Middle Eastern (MID) AF: 0.0347 AC: 10 AN: 288

European-Non Finnish (NFE) AF: 0.0716 AC: 4853 AN: 67816

Other (OTH) AF: 0.0561 AC: 118 AN: 2104

Alfa AF: 0.0643 Hom.: 62

Bravo AF: 0.0588

Asia WGS AF: 0.0130 AC: 45 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		2.0
PromoterAI		-0.0083	Neutral
Mutation Taster		=300/0	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: rs35123420; hg19: chr20-6748599;