chr6-24559205-A-G

Position:

• chr6-24559205-A-G

Variant summary

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

The NM_014809.4(KIAA0319):​c.2592-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,588,724 control chromosomes in the GnomAD database, including 138,371 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 0.33 (10042 hom., cov: 32)
  • Exomes 𝑓: 0.41 (128329 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2592-50T>C		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2592-50T>C		intron_variant		1	NM_014809.4	ENSP00000367459	P2

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49788 AN: 151976 Hom.: 10051 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.339

GnomAD3 exomes AF: 0.369 AC: 87483 AN: 236832 Hom.: 17962 AF XY: 0.383 AC XY: 48908 AN XY: 127664

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.220

Gnomad SAS exome AF: 0.335

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.414 AC: 595218 AN: 1436630 Hom.: 128329 Cov.: 28 AF XY: 0.415 AC XY: 295901 AN XY: 712752

Gnomad4 AFR exome AF: 0.0792

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.442

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.327 AC: 49762 AN: 152094 Hom.: 10042 Cov.: 32 AF XY: 0.326 AC XY: 24251 AN XY: 74328

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.338

Alfa AF: 0.430 Hom.: 18010

Bravo AF: 0.309

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.020
DANN	Benign	0.21

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: rs3903801; hg19: chr6-24559433; COSMIC: COSV65497781;