rs940187028

Variant names:

• chr12-45050684-G-T
• rs940187028
• NM_001004329.3:c.244C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-45050684-G-T
• chr12-45050684-G-A
• chr12-45050684-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001004329.3(DBX2):​c.244C>A​(p.Pro82Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,389,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DBX2 NM_001004329.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

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]

DBX2-AS1 (HGNC:55479): (DBX2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004329.3. 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
	DBX2	NM_001004329.3	MANE Select	c.244C>A	p.Pro82Thr	missense	Exon 1 of 4	NP_001004329.2	Q6ZNG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBX2	ENST00000332700.6	TSL:2 MANE Select	c.244C>A	p.Pro82Thr	missense	Exon 1 of 4	ENSP00000331470.6	Q6ZNG2
	DBX2-AS1	ENST00000829188.1		n.140+140G>T		intron	N/A
	DBX2-AS1	ENST00000829190.1		n.180+140G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389930 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 685532

African (AFR) AF: 0.00 AC: 0 AN: 30168

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24728

East Asian (EAS) AF: 0.00 AC: 0 AN: 34720

South Asian (SAS) AF: 0.00 AC: 0 AN: 78774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5308

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1075782

Other (OTH) AF: 0.00 AC: 0 AN: 57580

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.28
Sift	Benign	0.18	T
Sift4G	Benign	0.33	T
Polyphen		0.44	B
Vest4		0.54
MutPred		0.53		Gain of phosphorylation at P82 (P = 0.0534)
MVP		0.38
MPC		0.54
ClinPred		0.40	T
GERP RS		1.1
PromoterAI		-0.046	Neutral
Varity_R		0.10
gMVP		0.52
Mutation Taster		=91/9	polymorphism

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: rs940187028; hg19: chr12-45444467;