X-45151862-C-A

Variant names:

• chrX-45151862-C-A
• rs142916210
• NM_176819.4:c.1092G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176819.4(DIPK2B):​c.1092G>T​(p.Lys364Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,332 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K364K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08808774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.1092G>T	p.Lys364Asn	missense_variant	Exon 5 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	XM_005272670.1	c.918G>T	p.Lys306Asn	missense_variant	Exon 4 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.840G>T	p.Lys280Asn	missense_variant	Exon 4 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.1092G>T	p.Lys364Asn	missense_variant	Exon 5 of 5	5	NM_176819.4	ENSP00000381086.2
DIPK2B	ENST00000477281.1	n.390G>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097332 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362802

African (AFR) AF: 0.00 AC: 0 AN: 26392

American (AMR) AF: 0.00 AC: 0 AN: 35125

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19371

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30186

South Asian (SAS) AF: 0.00 AC: 0 AN: 53966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40479

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841623

Other (OTH) AF: 0.00 AC: 0 AN: 46053

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	14
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.0050
PROVEAN	Benign	0.85	N
REVEL	Benign	0.033
Sift	Benign	0.62	T
Sift4G	Benign	0.53	T
Vest4		0.098
MutPred		0.34		Gain of sheet (P = 0.0266);
MVP		0.77
MPC		0.26
ClinPred		0.28	T
GERP RS		3.4
gMVP		0.44
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142916210; hg19: chrX-45011107;