chrX-45191936-A-G

Variant names:

• chrX-45191936-A-G
• rs200347329
• NM_176819.4:c.313T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_176819.4(DIPK2B):​c.313T>C​(p.Ser105Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,210,312 control chromosomes in the GnomAD database, including 6 homozygotes. There are 568 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., 24 hem., cov: 23)
  • Exomes 𝑓: 0.00092 (6 hom. 544 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.867
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007990241).
• BP6: Variant X-45191936-A-G is Benign according to our data. Variant chrX-45191936-A-G is described in ClinVar as [Benign]. Clinvar id is 3046016.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2

Frequencies

GnomAD3 genomes AF: 0.000490 AC: 55 AN: 112186 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

Gnomad ASJ AF: 0.000378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00997

Gnomad FIN AF: 0.000487

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000394

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00154 AC: 283 AN: 183232 AF XY: 0.00253

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000924 AC: 1015 AN: 1098073 Hom.: 6 Cov.: 32 AF XY: 0.00150 AC XY: 544 AN XY: 363427

African (AFR) AF: 0.0000379 AC: 1 AN: 26401

American (AMR) AF: 0.0000852 AC: 3 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 6 AN: 19384

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30205

South Asian (SAS) AF: 0.0126 AC: 682 AN: 54137

European-Finnish (FIN) AF: 0.000395 AC: 16 AN: 40528

Middle Eastern (MID) AF: 0.00290 AC: 12 AN: 4137

European-Non Finnish (NFE) AF: 0.000295 AC: 248 AN: 841984

Other (OTH) AF: 0.000976 AC: 45 AN: 46091

GnomAD4 genome AF: 0.000499 AC: 56 AN: 112239 Hom.: 0 Cov.: 23 AF XY: 0.000697 AC XY: 24 AN XY: 34439

African (AFR) AF: 0.00 AC: 0 AN: 30876

American (AMR) AF: 0.000188 AC: 2 AN: 10647

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 1 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.0104 AC: 28 AN: 2701

European-Finnish (FIN) AF: 0.000487 AC: 3 AN: 6162

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.000394 AC: 21 AN: 53237

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.000381 Hom.: 19

Bravo AF: 0.000212

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00211 AC: 256

EpiCase AF: 0.000491

EpiControl AF: 0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DIPK2B-related disorder Benign:1

Oct 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.77	T;T
MetaRNN	Benign	0.0080	T;T
MetaSVM	Benign	-0.89	T
PhyloP100		0.87
PROVEAN	Benign	-1.5	N;D
REVEL	Benign	0.11
Sift	Benign	0.18	T;D
Sift4G	Benign	0.17	T;D
Vest4		0.16
MVP		0.65
MPC		0.73
ClinPred		0.077	T
GERP RS		4.3
gMVP		0.77
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs200347329; hg19: chrX-45051181;