X-45200617-C-G

Variant names:

• chrX-45200617-C-G
• rs199723553
• NM_176819.4:c.210G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_176819.4(DIPK2B):​c.210G>C​(p.Lys70Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,210,671 control chromosomes in the GnomAD database, including 3 homozygotes. There are 146 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (2 hom., 29 hem., cov: 23)
  • Exomes 𝑓: 0.00037 (1 hom. 117 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009176999).
• BP6: Variant X-45200617-C-G is Benign according to our data. Variant chrX-45200617-C-G is described in ClinVar as [Benign]. Clinvar id is 722221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000645 (73/113190) while in subpopulation EAS AF = 0.0191 (69/3605). AF 95% confidence interval is 0.0155. There are 2 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 5	5	NM_176819.4	ENSP00000381086.2
DIPK2B	ENST00000377934.4	c.210G>C	p.Lys70Asn	missense_variant	Exon 1 of 3	1		ENSP00000367168.4
ENSG00000229491	ENST00000438181.5	n.179+17188C>G		intron_variant	Intron 1 of 3	3
ENSG00000229491	ENST00000450527.5	n.94+17273C>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.000645 AC: 73 AN: 113139 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.000359

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000656

GnomAD2 exomes AF: 0.00173 AC: 317 AN: 182813 AF XY: 0.00150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0224

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.000444

GnomAD4 exome AF: 0.000373 AC: 409 AN: 1097481 Hom.: 1 Cov.: 30 AF XY: 0.000322 AC XY: 117 AN XY: 362849

African (AFR) AF: 0.00 AC: 0 AN: 26380

American (AMR) AF: 0.00 AC: 0 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.0122 AC: 367 AN: 30203

South Asian (SAS) AF: 0.000166 AC: 9 AN: 54072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40529

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841545

Other (OTH) AF: 0.000630 AC: 29 AN: 46065

GnomAD4 genome AF: 0.000645 AC: 73 AN: 113190 Hom.: 2 Cov.: 23 AF XY: 0.000821 AC XY: 29 AN XY: 35340

African (AFR) AF: 0.00 AC: 0 AN: 31264

American (AMR) AF: 0.000186 AC: 2 AN: 10751

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.0191 AC: 69 AN: 3605

South Asian (SAS) AF: 0.000360 AC: 1 AN: 2776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6257

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53434

Other (OTH) AF: 0.000649 AC: 1 AN: 1542

Alfa AF: 0.000181 Hom.: 4

Bravo AF: 0.000876

ExAC AF: 0.00154 AC: 187

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.0092	T;T
MetaSVM	Benign	-0.50	T
PhyloP100		4.2
PROVEAN	Benign	-1.6	N;D
REVEL	Benign	0.17
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.0080	D;D
Vest4		0.25
MutPred		0.42		Loss of methylation at K70 (P = 2e-04);Loss of methylation at K70 (P = 2e-04);
MVP		0.94
MPC		0.86
ClinPred		0.055	T
GERP RS		5.1
PromoterAI		-0.0050	Neutral
gMVP		0.75
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199723553; hg19: chrX-45059862; COSMIC: COSV65005596;