rs807541

chr6-24559053-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014809.4(KIAA0319):c.2694T>C(p.Ala898=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,612,098 control chromosomes in the GnomAD database, including 40,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2956 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37469 hom.)
• Consequence: KIAA0319 NM_014809.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-24559053-A-G is Benign according to our data. Variant chr6-24559053-A-G is described in ClinVar as [Benign]. Clinvar id is 3060711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.2694T>C	p.Ala898=	synonymous_variant	17/21	ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2694T>C	p.Ala898=	synonymous_variant	17/21	1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29112 AN: 152080 Hom.: 2948 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.201 AC: 50042 AN: 248788 Hom.: 5268 AF XY: 0.204 AC XY: 27372 AN XY: 134430

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.135

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.223 AC: 325627 AN: 1459900 Hom.: 37469 Cov.: 33 AF XY: 0.223 AC XY: 161734 AN XY: 726128

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.191 AC: 29144 AN: 152198 Hom.: 2956 Cov.: 33 AF XY: 0.188 AC XY: 14012 AN XY: 74400

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.189

Alfa AF: 0.208 Hom.: 5692

Bravo AF: 0.187

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KIAA0319-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.2
Dann	Benign	0.48

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: rs807541; hg19: chr6-24559281; COSMIC: COSV65498588;