6-24554534-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014809.4(KIAA0319):c.2948+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,602,474 control chromosomes in the GnomAD database, including 49,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7878 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41580 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, intron
• Scores: Splicing: ADA: 0.00009128
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-24554534-T-C is Benign according to our data. Variant chr6-24554534-T-C is described in ClinVar as [Benign]. Clinvar id is 3060264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0319	NM_014809.4	c.2948+7A>G		splice_region_variant, intron_variant		ENST00000378214.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2948+7A>G		splice_region_variant, intron_variant		1	NM_014809.4	P2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44619 AN: 151992 Hom.: 7858 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.225 AC: 56430 AN: 251072 Hom.: 7309 AF XY: 0.223 AC XY: 30308 AN XY: 135670

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.239

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.232 AC: 336492 AN: 1450364 Hom.: 41580 Cov.: 29 AF XY: 0.231 AC XY: 166962 AN XY: 722298

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.294 AC: 44674 AN: 152110 Hom.: 7878 Cov.: 32 AF XY: 0.291 AC XY: 21647 AN XY: 74396

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.276

Alfa AF: 0.235 Hom.: 10340

Bravo AF: 0.299

Asia WGS AF: 0.214 AC: 743 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 17, 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	-0.88
Cadd	Benign	2.7
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000091
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs2243831; hg19: chr6-24554762; COSMIC: COSV65497109;