rs2817200

Positions:

• chr6-24584138-A-G
• chr6-24584138-A-T

Variant summary

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

The NM_014809.4(KIAA0319):​c.995-436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,930 control chromosomes in the GnomAD database, including 9,583 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 0.35 (9583 hom., cov: 30)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.995-436T>C		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.995-436T>C		intron_variant		1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.995-436T>C		intron_variant		1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.968-436T>C		intron_variant		2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.860-436T>C		intron_variant		2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52748 AN: 151812 Hom.: 9577 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.347 AC: 52783 AN: 151930 Hom.: 9583 Cov.: 30 AF XY: 0.352 AC XY: 26151 AN XY: 74250

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.326

Alfa AF: 0.374 Hom.: 15431

Bravo AF: 0.333

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.84

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: rs2817200; hg19: chr6-24584366;