rs2744559

Variant names:

• chr6-24576403-C-T
• rs2744559
• NM_014809.4:c.1699G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.077 (1105 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1422 hom.)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15

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]

ACMG classification

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 rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1699G>A	p.Gly567Ser	missense_variant	Exon 10 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.1699G>A	p.Gly567Ser	missense_variant	Exon 10 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11742 AN: 152006 Hom.: 1099 Cov.: 32

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

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.: 31 AF XY: 0.0255 AC XY: 18573 AN XY: 727228

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.: 32 AF XY: 0.0741 AC XY: 5514 AN XY: 74366

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: 96

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: 59 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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.18
DEOGEN2	Benign	0.0030	.;.;.;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.78	T;T;T;.;T
MetaRNN	Benign	0.0015	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.47	.;N;.;N;N
PrimateAI	Benign	0.41	T
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	T
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

Other links and lift over

dbSNP: rs2744559; hg19: chr6-24576631;