rs2206525

Positions:

• chr6-24636675-A-G

Variant summary

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

The NM_014809.4(KIAA0319):​c.-106+9061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,162 control chromosomes in the GnomAD database, including 38,334 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 0.70 (38334 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.-106+9061T>C		intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+9061T>C		intron_variant		1	NM_014809.4	P2
KIAA0319	ENST00000537886.5	c.-106+9061T>C		intron_variant		1
KIAA0319	ENST00000430948.6	c.-81+8952T>C		intron_variant		2		A2
KIAA0319	ENST00000535378.5	c.-224+9061T>C		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107107 AN: 152044 Hom.: 38306 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.704 AC: 107186 AN: 152162 Hom.: 38334 Cov.: 32 AF XY: 0.701 AC XY: 52132 AN XY: 74372

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.716

Alfa AF: 0.672 Hom.: 4281

Bravo AF: 0.726

Asia WGS AF: 0.792 AC: 2750 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.63

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: rs2206525; hg19: chr6-24636903;