rs807535

chr6-24551501-T-C

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.2973A>G(p.Lys991=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,603,368 control chromosomes in the GnomAD database, including 15,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1133 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13909 hom.)
• Consequence: KIAA0319 NM_014809.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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=-0.84).
• BP6: Variant 6-24551501-T-C is Benign according to our data. Variant chr6-24551501-T-C is described in ClinVar as [Benign]. Clinvar id is 3059378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.2973A>G	p.Lys991=	synonymous_variant	20/21	ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2973A>G	p.Lys991=	synonymous_variant	20/21	1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17925 AN: 152040 Hom.: 1132 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.119 AC: 29890 AN: 251138 Hom.: 1897 AF XY: 0.120 AC XY: 16230 AN XY: 135746

Gnomad AFR exome AF: 0.0939

Gnomad AMR exome AF: 0.0961

Gnomad ASJ exome AF: 0.0740

Gnomad EAS exome AF: 0.0904

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.133 AC: 193517 AN: 1451210 Hom.: 13909 Cov.: 30 AF XY: 0.132 AC XY: 95534 AN XY: 722520

Gnomad4 AFR exome AF: 0.0913

Gnomad4 AMR exome AF: 0.0960

Gnomad4 ASJ exome AF: 0.0740

Gnomad4 EAS exome AF: 0.0595

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.118 AC: 17947 AN: 152158 Hom.: 1133 Cov.: 32 AF XY: 0.115 AC XY: 8533 AN XY: 74400

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.114

Alfa AF: 0.127 Hom.: 1660

Bravo AF: 0.115

Asia WGS AF: 0.0960 AC: 336 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.128

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

Dec 23, 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	-0.84
Cadd	Benign	2.2
Dann	Benign	0.40

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: rs807535; hg19: chr6-24551729; COSMIC: COSV65500550;