rs144500092

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-45191821-C-A
• chrX-45191821-C-G
• chrX-45191821-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_176819.4(DIPK2B):​c.428G>T​(p.Arg143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,210,636 control chromosomes in the GnomAD database, including 17 homozygotes. There are 391 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., 43 hem., cov: 23)
  • Exomes 𝑓: 0.0011 (14 hom. 348 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004731655).
• BP6: Variant X-45191821-C-A is Benign according to our data. Variant chrX-45191821-C-A is described in ClinVar as [Benign]. Clinvar id is 3033826.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00112 (1229/1098049) while in subpopulation AMR AF = 0.0307 (1081/35204). AF 95% confidence interval is 0.0292. There are 14 homozygotes in GnomAdExome4. There are 348 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.428G>T	p.Arg143Leu	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.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 173 AN: 112534 Hom.: 3 Cov.: 23

Gnomad AFR AF: 0.000388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.000735

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00395

GnomAD2 exomes AF: 0.00493 AC: 903 AN: 183149 AF XY: 0.00349

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00231

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00112 AC: 1229 AN: 1098049 Hom.: 14 Cov.: 33 AF XY: 0.000958 AC XY: 348 AN XY: 363405

African (AFR) AF: 0.000417 AC: 11 AN: 26399

American (AMR) AF: 0.0307 AC: 1081 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00182 AC: 55 AN: 30205

South Asian (SAS) AF: 0.000148 AC: 8 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: 0.0000226 AC: 19 AN: 841996

Other (OTH) AF: 0.00119 AC: 55 AN: 46095

GnomAD4 genome AF: 0.00155 AC: 174 AN: 112587 Hom.: 3 Cov.: 23 AF XY: 0.00124 AC XY: 43 AN XY: 34743

African (AFR) AF: 0.000387 AC: 12 AN: 31010

American (AMR) AF: 0.0136 AC: 146 AN: 10705

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

East Asian (EAS) AF: 0.00140 AC: 5 AN: 3571

South Asian (SAS) AF: 0.000737 AC: 2 AN: 2714

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53303

Other (OTH) AF: 0.00390 AC: 6 AN: 1538

Alfa AF: 0.000276 Hom.: 11

Bravo AF: 0.00323

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00330 AC: 401

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DIPK2B-related disorder Benign:1

Oct 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.88	D;D
MetaRNN	Benign	0.0047	T;T
MetaSVM	Benign	-0.91	T
PhyloP100		0.65
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.13
Sift	Benign	0.077	T;D
Sift4G	Benign	0.16	T;T
Vest4		0.14
MVP		0.55
MPC		0.52
ClinPred		0.031	T
GERP RS		3.0
gMVP		0.68
Mutation Taster		=91/9	polymorphism (auto)

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;