chrX-45191851-G-T

Variant names:

• chrX-45191851-G-T
• rs34834703
• NM_176819.4:c.398C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176819.4(DIPK2B):​c.398C>A​(p.Ala133Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,210,567 control chromosomes in the GnomAD database, including 89 homozygotes. There are 1,101 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (44 hom., 540 hem., cov: 24)
  • Exomes 𝑓: 0.0019 (45 hom. 561 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.750
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016578138).
• BP6: Variant X-45191851-G-T is Benign according to our data. Variant chrX-45191851-G-T is described in ClinVar as [Benign]. Clinvar id is 718331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.398C>A	p.Ala133Glu	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.398C>A	p.Ala133Glu	missense_variant	Exon 2 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.398C>A	p.Ala133Glu	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.398C>A	p.Ala133Glu	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.398C>A	p.Ala133Glu	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 1951 AN: 112396 Hom.: 44 Cov.: 24

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000367

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00517 AC: 947 AN: 183320 AF XY: 0.00335

Gnomad AFR exome AF: 0.0631

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00193 AC: 2120 AN: 1098117 Hom.: 45 Cov.: 33 AF XY: 0.00154 AC XY: 561 AN XY: 363471

African (AFR) AF: 0.0629 AC: 1661 AN: 26400

American (AMR) AF: 0.00378 AC: 133 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.000369 AC: 20 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00242 AC: 10 AN: 4136

European-Non Finnish (NFE) AF: 0.000127 AC: 107 AN: 842037

Other (OTH) AF: 0.00410 AC: 189 AN: 46095

GnomAD4 genome AF: 0.0175 AC: 1963 AN: 112450 Hom.: 44 Cov.: 24 AF XY: 0.0156 AC XY: 540 AN XY: 34620

African (AFR) AF: 0.0603 AC: 1862 AN: 30896

American (AMR) AF: 0.00524 AC: 56 AN: 10691

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6213

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53273

Other (OTH) AF: 0.0222 AC: 34 AN: 1532

Alfa AF: 0.00657 Hom.: 289

Bravo AF: 0.0201

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0576 AC: 221

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00568 AC: 690

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.77	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.90	T
PhyloP100		0.75
PROVEAN	Benign	-1.9	N;D
REVEL	Benign	0.080
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.031	D;D
Vest4		0.11
MVP		0.39
MPC		0.63
ClinPred		0.024	T
GERP RS		-0.41
gMVP		0.76
Mutation Taster		=92/8	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: rs34834703; hg19: chrX-45051096;