rs2745334

Variant names:

• chr6-24617302-C-T
• rs2745334
• NM_014809.4:c.-105-16094G>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.-105-16094G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 151,238 control chromosomes in the GnomAD database, including 586 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 0.084 (586 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-105-16094G>A		intron_variant	Intron 1 of 20	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-105-16094G>A		intron_variant	Intron 1 of 20	1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-105-16094G>A		intron_variant	Intron 1 of 18	1		ENSP00000439700.1
KIAA0319	ENST00000535378.5	c.-223-16094G>A		intron_variant	Intron 1 of 21	2		ENSP00000442403.1
KIAA0319	ENST00000430948.6	c.-80-20684G>A		intron_variant	Intron 1 of 19	2		ENSP00000401086.2

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12637 AN: 151120 Hom.: 586 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0836 AC: 12639 AN: 151238 Hom.: 586 Cov.: 32 AF XY: 0.0808 AC XY: 5964 AN XY: 73776

African (AFR) AF: 0.0717 AC: 2954 AN: 41174

American (AMR) AF: 0.0617 AC: 932 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5162

South Asian (SAS) AF: 0.0623 AC: 299 AN: 4796

European-Finnish (FIN) AF: 0.0813 AC: 839 AN: 10324

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6852 AN: 67902

Other (OTH) AF: 0.0886 AC: 186 AN: 2100

Alfa AF: 0.0980 Hom.: 285

Bravo AF: 0.0816

Asia WGS AF: 0.0360 AC: 126 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.60
PhyloP100		0.65
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: rs2745334; hg19: chr6-24617530;