rs2206525

Variant names:

• chr6-24636675-A-G
• rs2206525
• NM_014809.4:c.-106+9061T>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.-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
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.-106+9061T>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-106+8952T>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-106+9360T>C		intron	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.-106+9061T>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+9061T>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000535378.5	TSL:2	c.-224+9061T>C		intron	N/A	ENSP00000442403.1

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

African (AFR) AF: 0.797 AC: 33072 AN: 41518

American (AMR) AF: 0.772 AC: 11798 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2209 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4524 AN: 5180

South Asian (SAS) AF: 0.693 AC: 3348 AN: 4828

European-Finnish (FIN) AF: 0.537 AC: 5678 AN: 10570

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44085 AN: 67988

Other (OTH) AF: 0.716 AC: 1515 AN: 2116

Alfa AF: 0.676 Hom.: 4516

Bravo AF: 0.726

Asia WGS AF: 0.792 AC: 2750 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.63
PhyloP100		-0.54
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: rs2206525; hg19: chr6-24636903;