chrX-45191866-C-A

Variant names:

• chrX-45191866-C-A
• rs1132201
• NM_176819.4:c.383G>T

Variant summary

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

The NM_176819.4(DIPK2B):​c.383G>T​(p.Arg128Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R128K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 28 publications found

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]

ENSG00000229491 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
DIPK2B	NM_176819.4	c.383G>T	p.Arg128Ile	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.383G>T	p.Arg128Ile	missense_variant	Exon 2 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.383G>T	p.Arg128Ile	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.383G>T	p.Arg128Ile	missense_variant	Exon 2 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.383G>T	p.Arg128Ile	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.98
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.78	T
PhyloP100		1.2
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.14
Sift	Benign	0.035	D;D
Sift4G	Uncertain	0.047	D;D
Vest4		0.58
MutPred		0.30		Loss of disorder (P = 0.0449);Loss of disorder (P = 0.0449);
MVP		0.80
MPC		0.90
ClinPred		0.82	D
GERP RS		2.9
gMVP		0.73
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1132201; hg19: chrX-45051111;