chrX-45154180-C-T

Position:

• chrX-45154180-C-T

Variant summary

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

The NM_176819.4(DIPK2B):​c.691G>A​(p.Gly231Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 21)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.55

Genes affected

DIPK2B (HGNC:25866): (divergent protein kinase domain 2B) Predicted to be located in extracellular region. [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/exons	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.691G>A	p.Gly231Arg	missense_variant	4/5	ENST00000398000.7	NP_789789.2
DIPK2B	XM_005272670.1	c.517G>A	p.Gly173Arg	missense_variant	3/4		XP_005272727.1
DIPK2B	XM_006724559.1	c.517G>A	p.Gly173Arg	missense_variant	3/4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.691G>A	p.Gly231Arg	missense_variant	4/5	5	NM_176819.4	ENSP00000381086.2
DIPK2B	ENST00000477281.1	n.88-99G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

DIPK2B-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2024

The DIPK2B c.691G>A variant is predicted to result in the amino acid substitution p.Gly231Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.63	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.82
MutPred		0.46		Gain of solvent accessibility (P = 0.0097);
MVP		0.63
MPC		0.91
ClinPred		1.0	D
GERP RS		5.4
gMVP		0.83

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: rs2046977751; hg19: chrX-45013425;