Variant 9-5919754-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001017969.3(KIAA2026):c.6242G>A(p.Arg2081Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

KIAA2026
NM_001017969.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008494079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA2026	NM_001017969.3 linkuse as main transcript	c.6242G>A	p.Arg2081Gln	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.6242G>A	p.Arg2081Gln	missense_variant	8/8	5	NM_001017969.3	P4	Q5HYC2-1
KIAA2026	ENST00000381461.6 linkuse as main transcript	c.6152G>A	p.Arg2051Gln	missense_variant	7/7	5		A2	Q5HYC2-2
KIAA2026	ENST00000436015.6 linkuse as main transcript	c.554+790G>A		intron_variant, NMD_transcript_variant		3
KIAA2026	ENST00000540714.1 linkuse as main transcript	c.*3829G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000544

AC:

135

AN:

248066

Hom.:

AF XY:

0.000587

AC XY:

AN XY:

134562

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.000459

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000970

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000823

AC:

1202

AN:

1461210

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

539

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000532

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00832

Hom.:

824

Bravo

AF:

0.000529

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.000497

AC:

Asia WGS

AF:

0.000577

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

Oct 27, 2021

The c.6242G>A (p.R2081Q) alteration is located in exon 8 (coding exon 8) of the KIAA2026 gene. This alteration results from a G to A substitution at nucleotide position 6242, causing the arginine (R) at amino acid position 2081 to be replaced by a glutamine (Q). 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

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.018

Sift

Benign

0.45

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0070

B;.

Vest4

0.11

MVP

0.10

ClinPred

0.0085

GERP RS

1.5

Varity_R

0.030

gMVP

0.063

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