rs2744564

Positions:

• chr6-24579985-C-G

Variant summary

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

The NM_014809.4(KIAA0319):​c.1280-35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,462,394 control chromosomes in the GnomAD database, including 2,171 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 0.072 (935 hom., cov: 31)
  • Exomes 𝑓: 0.028 (1236 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1280-35G>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.1280-35G>C		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10860 AN: 152024 Hom.: 930 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0589

GnomAD3 exomes AF: 0.0264 AC: 4449 AN: 168250 Hom.: 257 AF XY: 0.0218 AC XY: 1932 AN XY: 88630

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.00612

Gnomad EAS exome AF: 0.000965

Gnomad SAS exome AF: 0.00203

Gnomad FIN exome AF: 0.00349

Gnomad NFE exome AF: 0.0231

Gnomad OTH exome AF: 0.0203

GnomAD4 exome AF: 0.0276 AC: 36176 AN: 1310252 Hom.: 1236 Cov.: 19 AF XY: 0.0261 AC XY: 17015 AN XY: 652432

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.00683

Gnomad4 EAS exome AF: 0.000467

Gnomad4 SAS exome AF: 0.00241

Gnomad4 FIN exome AF: 0.00332

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0335

GnomAD4 genome AF: 0.0716 AC: 10897 AN: 152142 Hom.: 935 Cov.: 31 AF XY: 0.0684 AC XY: 5091 AN XY: 74394

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0410 Hom.: 82

Bravo AF: 0.0811

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.32

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: rs2744564; hg19: chr6-24580213;