rs750113512

Variant names:

• chr12-45050629-C-A
• rs750113512
• NM_001004329.3:c.299G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-45050629-C-A
• chr12-45050629-C-G
• chr12-45050629-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004329.3(DBX2):​c.299G>T​(p.Gly100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G100E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DBX2 NM_001004329.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

DBX2 (HGNC:33186): (developing brain homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBX2	NM_001004329.3	c.299G>T	p.Gly100Val	missense_variant	Exon 1 of 4	ENST00000332700.6	NP_001004329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBX2	ENST00000332700.6	c.299G>T	p.Gly100Val	missense_variant	Exon 1 of 4	2	NM_001004329.3	ENSP00000331470.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397842 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 689584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.46
Sift	Benign	0.18	T
Sift4G	Benign	0.52	T
Polyphen		0.76	P
Vest4		0.52
MutPred		0.66		Loss of disorder (P = 0.0926);
MVP		0.52
MPC		0.28
ClinPred		0.24	T
GERP RS		3.1
Varity_R		0.12
gMVP		0.36

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: rs750113512; hg19: chr12-45444412;