rs2744605

Positions:

• chr6-24544104-G-A

Variant summary

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

The ENST00000537886.5(KIAA0319):​c.*3061C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,228 control chromosomes in the GnomAD database, including 715 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 0.081 (715 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: KIAA0319 ENST00000537886.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.*3061C>T		downstream_gene_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.*3061C>T		downstream_gene_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12301 AN: 152110 Hom.: 712 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00941

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0750

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0809 AC: 12314 AN: 152228 Hom.: 715 Cov.: 33 AF XY: 0.0825 AC XY: 6139 AN XY: 74414

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.00943

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0479 Hom.: 237

Bravo AF: 0.0787

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2744605; hg19: chr6-24544332;