Genetic Variant DIPK2B:c.499-7C>A (chrX-45157895-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_176819.4(DIPK2B):c.499-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,023,919 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.0000059 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

DIPK2B
NM_176819.4 splice_region, intron

Scores

Splicing: ADA: 0.9993

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.209

Publications

0 publications found

Variant links:

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]

DIPK2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.499-7C>A	splice_region_variant, intron_variant	Intron 2 of 4	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	XM_005272670.1 link	c.499-3697C>A	intron_variant	Intron 2 of 3		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.499-3697C>A	intron_variant	Intron 2 of 3		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 link	c.499-7C>A		splice_region_variant, intron_variant	Intron 2 of 4	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1
DIPK2B	ENST00000477281.1 link	n.88-3814C>A		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

104974

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000988

AC:

AN:

101205

AF XY:

0.0000314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000263

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000586

AC:

AN:

1023919

Hom.:

Cov.:

AF XY:

0.00000311

AC XY:

AN XY:

321819

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24435

American (AMR)

AF:

0.00

AC:

AN:

27308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18055

East Asian (EAS)

AF:

0.00

AC:

AN:

26416

South Asian (SAS)

AF:

0.00

AC:

AN:

46859

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2769

European-Non Finnish (NFE)

AF:

0.00000749

AC:

AN:

801275

Other (OTH)

AF:

0.00

AC:

AN:

42956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

104974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27638

African (AFR)

AF:

0.00

AC:

AN:

28628

American (AMR)

AF:

0.00

AC:

AN:

9748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2558

East Asian (EAS)

AF:

0.00

AC:

AN:

3283

South Asian (SAS)

AF:

0.00

AC:

AN:

2236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

227

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50975

Other (OTH)

AF:

0.00

AC:

AN:

1383

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.8

(source)

DANN

Benign

0.39

PhyloP100

-0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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X-45157895-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over