X-45191821-C-T

Variant names:

• chrX-45191821-C-T
• rs144500092
• NM_176819.4:c.428G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_176819.4(DIPK2B):​c.428G>A​(p.Arg143His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,210,583 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 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. R143L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000017 (0 hom. 4 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10554266).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176819.4. 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
	DIPK2B	NM_176819.4	MANE Select	c.428G>A	p.Arg143His	missense	Exon 2 of 5	NP_789789.2
	DIPK2B	NM_024689.3		c.428G>A	p.Arg143His	missense	Exon 2 of 3	NP_078965.2	Q9H7Y0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIPK2B	ENST00000398000.7	TSL:5 MANE Select	c.428G>A	p.Arg143His	missense	Exon 2 of 5	ENSP00000381086.2	Q9H7Y0-1
	DIPK2B	ENST00000377934.4	TSL:1	c.428G>A	p.Arg143His	missense	Exon 2 of 3	ENSP00000367168.4	Q9H7Y0-2
	DIPK2B	ENST00000905163.1		c.428G>A	p.Arg143His	missense	Exon 2 of 5	ENSP00000575222.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112534 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183149 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000173 AC: 19 AN: 1098049 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 4 AN XY: 363405

African (AFR) AF: 0.0000758 AC: 2 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54139

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.0000178 AC: 15 AN: 841996

Other (OTH) AF: 0.0000217 AC: 1 AN: 46095

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112534 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34680

African (AFR) AF: 0.0000323 AC: 1 AN: 30942

American (AMR) AF: 0.00 AC: 0 AN: 10692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53310

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.00 Hom.: 11

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.97
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.65
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.097
Sift	Benign	0.080	T
Sift4G	Benign	0.14	T
Vest4		0.054
MutPred		0.28		Loss of MoRF binding (P = 0.0098)
MVP		0.53
MPC		0.28
ClinPred		0.20	T
GERP RS		3.0
gMVP		0.47
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: rs144500092; hg19: chrX-45051066; COSMIC: COSV107479914;