rs2817245

Variant names:

• chr6-24547378-G-A
• rs2817245
• NM_014809.4:c.3041-35C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24547378-G-A
• chr6-24547378-G-T

Variant summary

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

The NM_014809.4(KIAA0319):​c.3041-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,579,254 control chromosomes in the GnomAD database, including 28,854 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 0.23 (4698 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24156 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 11 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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.3041-35C>T		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.3041-35C>T		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.3041-35C>T		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.3041-35C>T		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2858-35C>T		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.1274-35C>T		intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34831 AN: 152016 Hom.: 4676 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.188 AC: 43143 AN: 229864 AF XY: 0.188

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.179 AC: 255581 AN: 1427118 Hom.: 24156 Cov.: 25 AF XY: 0.179 AC XY: 127241 AN XY: 709208

African (AFR) AF: 0.379 AC: 12411 AN: 32774

American (AMR) AF: 0.141 AC: 6045 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4882 AN: 25778

East Asian (EAS) AF: 0.0924 AC: 3602 AN: 38978

South Asian (SAS) AF: 0.209 AC: 17729 AN: 84714

European-Finnish (FIN) AF: 0.231 AC: 12098 AN: 52292

Middle Eastern (MID) AF: 0.287 AC: 1629 AN: 5680

European-Non Finnish (NFE) AF: 0.171 AC: 185957 AN: 1084898

Other (OTH) AF: 0.190 AC: 11228 AN: 59172

GnomAD4 genome AF: 0.229 AC: 34887 AN: 152136 Hom.: 4698 Cov.: 32 AF XY: 0.231 AC XY: 17171 AN XY: 74368

African (AFR) AF: 0.372 AC: 15430 AN: 41480

American (AMR) AF: 0.174 AC: 2667 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5174

South Asian (SAS) AF: 0.196 AC: 943 AN: 4808

European-Finnish (FIN) AF: 0.235 AC: 2493 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11524 AN: 68008

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.185 Hom.: 2879

Bravo AF: 0.231

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		0.18
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: rs2817245; hg19: chr6-24547606;