Variant 9-5919734-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001017969.3(KIAA2026):c.6262C>T(p.Pro2088Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00146 in 1,613,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

KIAA2026
NM_001017969.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

KIAA2026 (HGNC:23378): (bromodomain containing 10)

KIAA2026 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.154977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA2026	NM_001017969.3 linkuse as main transcript	c.6262C>T	p.Pro2088Ser	missense_variant	8/8	ENST00000399933.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA2026	ENST00000399933.8 linkuse as main transcript	c.6262C>T	p.Pro2088Ser	missense_variant	8/8	5	NM_001017969.3	P4	Q5HYC2-1
KIAA2026	ENST00000381461.6 linkuse as main transcript	c.6172C>T	p.Pro2058Ser	missense_variant	7/7	5		A2	Q5HYC2-2
KIAA2026	ENST00000436015.6 linkuse as main transcript	c.554+810C>T		intron_variant, NMD_transcript_variant		3
KIAA2026	ENST00000540714.1 linkuse as main transcript	c.*3849C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00101

AC:

249

AN:

247150

Hom.:

AF XY:

0.00110

AC XY:

147

AN XY:

134050

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000468

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.00177

Gnomad FIN exome

AF:

0.000606

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00153

AC:

2239

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1126

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000382

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00171

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000815

AC:

124

AN:

152218

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000268

AC:

ESP6500EA

AF:

0.00146

AC:

ExAC

AF:

0.000993

AC:

120

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.6262C>T (p.P2088S) alteration is located in exon 8 (coding exon 8) of the KIAA2026 gene. This alteration results from a C to T substitution at nucleotide position 6262, causing the proline (P) at amino acid position 2088 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

0.080

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

0.53

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

1.0

D;.

Vest4

0.77

MVP

0.44

ClinPred

0.058

GERP RS

5.0

Varity_R

0.31

gMVP

0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over