Variant rs2744559 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014809.4(KIAA0319):c.1699G>A(p.Gly567Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0318 in 1,613,952 control chromosomes in the GnomAD database, including 2,527 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.077 ( 1105 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1422 hom. )

Consequence

KIAA0319
NM_014809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.15

Variant links:

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

KIAA0319 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015474856).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4 linkuse as main transcript	c.1699G>A	p.Gly567Ser	missense_variant	10/21	ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8 linkuse as main transcript	c.1699G>A	p.Gly567Ser	missense_variant	10/21	1	NM_014809.4	P2	Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.0772

AC:

11742

AN:

152006

Hom.:

1099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0617

GnomAD3 exomes

AF:

0.0287

AC:

7221

AN:

251360

Hom.:

483

AF XY:

0.0237

AC XY:

3213

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0271

AC:

39611

AN:

1461828

Hom.:

1422

Cov.:

AF XY:

0.0255

AC XY:

18573

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.00240

Gnomad4 FIN exome

AF:

0.00314

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0774

AC:

11779

AN:

152124

Hom.:

1105

Cov.:

AF XY:

0.0741

AC XY:

5514

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00302

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0611

Alfa

AF:

0.0319

Hom.:

491

Bravo

AF:

0.0877

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0270

AC:

104

ESP6500AA

AF:

0.225

AC:

991

ESP6500EA

AF:

0.0210

AC:

181

ExAC

AF:

0.0326

AC:

3960

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0198

EpiControl

AF:

0.0204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.0030

.;.;.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

T;T;T;.;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.47

.;N;.;N;N

MutationTaster

Benign

0.52

P;P;P;P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

0.62

N;N;N;N;N

REVEL

Benign

0.076

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.027, 0.034

.;.;B;B;B

Vest4

0.055

MPC

0.12

ClinPred

0.015

GERP RS

3.0

Varity_R

0.091

gMVP

0.30

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over