rs2760164

Variant names:

• chr6-24564345-G-A
• rs2760164
• NM_014809.4:c.2293-5C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.2293-5C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00002193
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2293-5C>T		splice_region_variant, intron_variant	Intron 14 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2293-5C>T		splice_region_variant, intron_variant	Intron 14 of 20	1	NM_014809.4	ENSP00000367459.3

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

GnomAD2 exomes AF: 0.0208 AC: 5194 AN: 249640 AF XY: 0.0180

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 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

African (AFR) AF: 0.145 AC: 4843 AN: 33312

American (AMR) AF: 0.0132 AC: 590 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26132

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.00187 AC: 161 AN: 86246

European-Finnish (FIN) AF: 0.00341 AC: 182 AN: 53410

Middle Eastern (MID) AF: 0.0199 AC: 115 AN: 5766

European-Non Finnish (NFE) AF: 0.0236 AC: 26169 AN: 1110248

Other (OTH) AF: 0.0255 AC: 1541 AN: 60340

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

African (AFR) AF: 0.137 AC: 5677 AN: 41514

American (AMR) AF: 0.0224 AC: 343 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1409 AN: 68022

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0336 Hom.: 144

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
PhyloP100		1.4
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2760164; hg19: chr6-24564573;