rs2760163

Variant names:

• chr6-24564351-A-G
• rs2760163
• NM_014809.4:c.2293-11T>C

Variant summary

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

The NM_014809.4(KIAA0319):​c.2293-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,612,004 control chromosomes in the GnomAD database, including 1,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.050 (421 hom., cov: 32)
  • Exomes 𝑓: 0.023 (792 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Scores: Splicing: ADA: 0.05520
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.2293-11T>C		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2293-11T>C		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2293-11T>C		intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2293-11T>C		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2293-11T>C		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.526-11T>C		intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7570 AN: 152152 Hom.: 419 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: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0420

GnomAD2 exomes AF: 0.0208 AC: 5190 AN: 249516 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: 0.0230 AC: 33585 AN: 1459734 Hom.: 792 Cov.: 31 AF XY: 0.0219 AC XY: 15922 AN XY: 726272

African (AFR) AF: 0.145 AC: 4827 AN: 33292

American (AMR) AF: 0.0132 AC: 590 AN: 44718

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: 0.00343 AC: 183 AN: 53404

Middle Eastern (MID) AF: 0.0196 AC: 113 AN: 5762

European-Non Finnish (NFE) AF: 0.0235 AC: 26110 AN: 1110146

Other (OTH) AF: 0.0254 AC: 1534 AN: 60334

GnomAD4 genome AF: 0.0498 AC: 7577 AN: 152270 Hom.: 421 Cov.: 32 AF XY: 0.0468 AC XY: 3482 AN XY: 74456

African (AFR) AF: 0.137 AC: 5671 AN: 41510

American (AMR) AF: 0.0224 AC: 343 AN: 15298

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: 0.00320 AC: 34 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0207 AC: 1409 AN: 68032

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0396 Hom.: 99

Bravo AF: 0.0561

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.055
dbscSNV1_RF	Benign	0.19
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: rs2760163; hg19: chr6-24564579;