rs2760164

Positions:

• chr6-24564345-G-A
• chr6-24564345-G-T

Variant summary

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

The NM_014809.4(KIAA0319):​c.2293-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,612,122 control chromosomes in the GnomAD database, including 1,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (422 hom., cov: 32)
  • Exomes 𝑓: 0.023 (793 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002193
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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 (BayesDel_noAF=-0.83).
• 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/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2293-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2293-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7576 AN: 152128 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0208 AC: 5194 AN: 249640 Hom.: 191 AF XY: 0.0180 AC XY: 2425 AN XY: 134954

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000871

Gnomad SAS exome AF: 0.00157

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0151

GnomAD4 exome AF: 0.0231 AC: 33668 AN: 1459876 Hom.: 793 Cov.: 31 AF XY: 0.0220 AC XY: 15962 AN XY: 726342

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.00187

Gnomad4 FIN exome AF: 0.00341

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0255

GnomAD4 genome AF: 0.0498 AC: 7583 AN: 152246 Hom.: 422 Cov.: 32 AF XY: 0.0468 AC XY: 3486 AN XY: 74440

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0310 Hom.: 99

Bravo AF: 0.0562

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0189

EpiControl AF: 0.0195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0
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: rs2760164; hg19: chr6-24564573;