6-24563324-C-T

Variant names:

• chr6-24563324-C-T
• rs2744549
• NM_014809.4:c.2591+35G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.2591+35G>A 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 1,578,904 control chromosomes in the GnomAD database, including 1,221 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 (435 hom., cov: 33)
  • Exomes 𝑓: 0.024 (786 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.2591+35G>A		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2591+35G>A		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2591+35G>A		intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2591+35G>A		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2591+35G>A		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.824+35G>A		intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7619 AN: 152164 Hom.: 433 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0217 AC: 5029 AN: 231992 AF XY: 0.0187

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.00184

Gnomad EAS exome AF: 0.000903

Gnomad FIN exome AF: 0.00339

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0239 AC: 34063 AN: 1426622 Hom.: 786 Cov.: 30 AF XY: 0.0228 AC XY: 16082 AN XY: 705114

African (AFR) AF: 0.147 AC: 4817 AN: 32674

American (AMR) AF: 0.0135 AC: 564 AN: 41832

Ashkenazi Jewish (ASJ) AF: 0.00186 AC: 46 AN: 24744

East Asian (EAS) AF: 0.000488 AC: 19 AN: 38912

South Asian (SAS) AF: 0.00213 AC: 172 AN: 80790

European-Finnish (FIN) AF: 0.00346 AC: 178 AN: 51394

Middle Eastern (MID) AF: 0.0214 AC: 120 AN: 5614

European-Non Finnish (NFE) AF: 0.0244 AC: 26596 AN: 1091766

Other (OTH) AF: 0.0263 AC: 1551 AN: 58896

GnomAD4 genome AF: 0.0501 AC: 7627 AN: 152282 Hom.: 435 Cov.: 33 AF XY: 0.0470 AC XY: 3500 AN XY: 74472

African (AFR) AF: 0.138 AC: 5717 AN: 41522

American (AMR) AF: 0.0225 AC: 344 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3464

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5194

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1410 AN: 68028

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0246 Hom.: 60

Bravo AF: 0.0563

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.68
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2744549; hg19: chr6-24563552;