rs2817195

Positions:

• chr6-24570116-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.1859-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,371,906 control chromosomes in the GnomAD database, including 1,099 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 0.050 (434 hom., cov: 32)
  • Exomes 𝑓: 0.023 (665 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.1859-81T>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.1859-81T>C		intron_variant		1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7613 AN: 152144 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0412

GnomAD4 exome AF: 0.0235 AC: 28660 AN: 1219644 Hom.: 665 AF XY: 0.0223 AC XY: 13533 AN XY: 607772

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.000487

Gnomad4 SAS exome AF: 0.00196

Gnomad4 FIN exome AF: 0.00330

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0500 AC: 7617 AN: 152262 Hom.: 434 Cov.: 32 AF XY: 0.0469 AC XY: 3495 AN XY: 74452

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0369 Hom.: 36

Bravo AF: 0.0561

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.84

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: rs2817195; hg19: chr6-24570344;