Genetic Variant NM_176819.4:c.499-4G>A (chrX-45157892-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_176819.4(DIPK2B):c.499-4G>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 0.000012 in 1,085,656 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000078 ( 0 hom., 2 hem., cov: 19)

Exomes 𝑓: 0.0000051 ( 0 hom. 4 hem. )

Consequence

DIPK2B
NM_176819.4 splice_region, intron

Scores

Splicing: ADA: 0.00001838

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.44

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.499-4G>A	splice_region_variant, intron_variant	Intron 2 of 4	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	XM_005272670.1 link	c.499-3694G>A	intron_variant	Intron 2 of 3		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.499-3694G>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.499-4G>A		splice_region_variant, intron_variant	Intron 2 of 4	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1
DIPK2B	ENST00000477281.1 link	n.88-3811G>A		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0000780

AC:

AN:

102514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000285

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:

0.0000103

AC:

AN:

97149

AF XY:

0.0000336

show subpopulations

Gnomad AFR exome

AF:

0.000184

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000509

AC:

AN:

983142

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

301658

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

23298

American (AMR)

AF:

0.00

AC:

AN:

25949

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16572

East Asian (EAS)

AF:

0.00

AC:

AN:

23200

South Asian (SAS)

AF:

0.00

AC:

AN:

46098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2559

European-Non Finnish (NFE)

AF:

0.00000129

AC:

AN:

774301

Other (OTH)

AF:

0.0000249

AC:

AN:

40219

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000780

AC:

AN:

102514

Hom.:

Cov.:

AF XY:

0.0000760

AC XY:

AN XY:

26306

show subpopulations

African (AFR)

AF:

0.000285

AC:

AN:

28102

American (AMR)

AF:

0.00

AC:

AN:

9375

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2518

East Asian (EAS)

AF:

0.00

AC:

AN:

3119

South Asian (SAS)

AF:

0.00

AC:

AN:

2074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4817

Middle Eastern (MID)

AF:

0.00

AC:

AN:

223

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50306

Other (OTH)

AF:

0.00

AC:

AN:

1352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.016

(source)

DANN

Benign

0.52

PhyloP100

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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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NM_176819.4:c.499-4G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over