rs2817195

Variant names:

• chr6-24570116-A-G
• rs2817195
• NM_014809.4:c.1859-81T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-24570116-A-G
• chr6-24570116-A-T

Variant summary

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

The ENST00000378214.8(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 ENST00000378214.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378214.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.1859-81T>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.1859-81T>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.1859-81T>C		intron	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1859-81T>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.1859-81T>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.92-81T>C		intron	N/A	ENSP00000483665.1

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

African (AFR) AF: 0.147 AC: 4192 AN: 28532

American (AMR) AF: 0.0139 AC: 502 AN: 36160

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 38 AN: 22024

East Asian (EAS) AF: 0.000487 AC: 18 AN: 36932

South Asian (SAS) AF: 0.00196 AC: 142 AN: 72332

European-Finnish (FIN) AF: 0.00330 AC: 156 AN: 47252

Middle Eastern (MID) AF: 0.0205 AC: 76 AN: 3704

European-Non Finnish (NFE) AF: 0.0241 AC: 22187 AN: 921066

Other (OTH) AF: 0.0261 AC: 1349 AN: 51642

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

African (AFR) AF: 0.137 AC: 5708 AN: 41536

American (AMR) AF: 0.0221 AC: 338 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0209 AC: 1420 AN: 68018

Other (OTH) AF: 0.0408 AC: 86 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.84
PhyloP100		2.0
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: rs2817195; hg19: chr6-24570344;