rs2744550

Variant names:

• chr6-24564316-T-C
• rs2744550
• NM_014809.4:c.2317A>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.2317A>G​(p.Ser773Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,302 control chromosomes in the GnomAD database, including 1,214 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 0.050 (421 hom., cov: 32)
  • Exomes 𝑓: 0.023 (793 hom.)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=0.001576066).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2317A>G	p.Ser773Gly	missense_variant	Exon 15 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2317A>G	p.Ser773Gly	missense_variant	Exon 15 of 21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7569 AN: 152092 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0417

GnomAD3 exomes AF: 0.0209 AC: 5230 AN: 250664 Hom.: 198 AF XY: 0.0180 AC XY: 2440 AN XY: 135500

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000870

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0151

GnomAD4 exome AF: 0.0234 AC: 34210 AN: 1461092 Hom.: 793 Cov.: 31 AF XY: 0.0223 AC XY: 16209 AN XY: 726902

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.00189

Gnomad4 FIN exome AF: 0.00343

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0498 AC: 7576 AN: 152210 Hom.: 421 Cov.: 32 AF XY: 0.0468 AC XY: 3481 AN XY: 74430

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0251 Hom.: 191

Bravo AF: 0.0561

TwinsUK AF: 0.0243 AC: 90

ALSPAC AF: 0.0257 AC: 99

ESP6500AA AF: 0.133 AC: 586

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0230 AC: 2794

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0189

EpiControl AF: 0.0196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.99
DANN	Benign	0.42
DEOGEN2	Benign	0.0095	.;.;.;.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.047	T;T;T;T;.;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	.;.;M;.;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	.;N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.42	.;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.0010, 0.0020	.;.;.;B;B;B
Vest4		0.052
MPC		0.098
ClinPred		0.0084	T
GERP RS		-1.5
Varity_R		0.057
gMVP		0.34

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: rs2744550; hg19: chr6-24564544;