chrX-45157892-C-G

Variant names:

• chrX-45157892-C-G
• rs758871668
• NM_176819.4:c.499-4G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_176819.4(DIPK2B):​c.499-4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 983,144 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: not found (cov: 19)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: DIPK2B NM_176819.4 splice_region, intron
• Scores: Splicing: ADA: 0.000009257
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.0000102 AC: 10 AN: 983144 Hom.: 0 Cov.: 31 AF XY: 0.00000995 AC XY: 3 AN XY: 301658

African (AFR) AF: 0.00 AC: 0 AN: 23298

American (AMR) AF: 0.00 AC: 0 AN: 25949

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16572

East Asian (EAS) AF: 0.00 AC: 0 AN: 23200

South Asian (SAS) AF: 0.00 AC: 0 AN: 46098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2559

European-Non Finnish (NFE) AF: 0.0000129 AC: 10 AN: 774303

Other (OTH) AF: 0.00 AC: 0 AN: 40219

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.013
DANN	Benign	0.41
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000093
dbscSNV1_RF	Benign	0.0020
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: rs758871668; hg19: chrX-45017137;