rs2817201

Variant names:

• chr6-24584986-C-A
• rs2817201
• NM_014809.4:c.995-1284G>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.995-1284G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,074 control chromosomes in the GnomAD database, including 39,763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39763 hom., cov: 31)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.995-1284G>T		intron_variant	Intron 4 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.995-1284G>T		intron_variant	Intron 4 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.995-1284G>T		intron_variant	Intron 4 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.968-1284G>T		intron_variant	Intron 5 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.860-1284G>T		intron_variant	Intron 3 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108659 AN: 151956 Hom.: 39740 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.690

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.715 AC: 108734 AN: 152074 Hom.: 39763 Cov.: 31 AF XY: 0.718 AC XY: 53401 AN XY: 74342

African (AFR) AF: 0.585 AC: 24226 AN: 41428

American (AMR) AF: 0.667 AC: 10189 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2670 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2767 AN: 5172

South Asian (SAS) AF: 0.765 AC: 3685 AN: 4820

European-Finnish (FIN) AF: 0.874 AC: 9258 AN: 10598

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53618 AN: 67996

Other (OTH) AF: 0.692 AC: 1457 AN: 2106

Alfa AF: 0.762 Hom.: 33147

Bravo AF: 0.694

Asia WGS AF: 0.670 AC: 2330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2817201; hg19: chr6-24585214;