rs2235676

Variant names:

• chr6-24645469-G-T
• rs2235676
• NM_014809.4:c.-106+267C>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.-106+267C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,190 control chromosomes in the GnomAD database, including 1,046 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 0.10 (1046 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 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.-106+267C>A		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.-106+158C>A		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.-106+566C>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.-106+267C>A		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+267C>A		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000901508.1		c.-106+566C>A		intron	N/A	ENSP00000571567.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15986 AN: 152072 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15973 AN: 152190 Hom.: 1046 Cov.: 32 AF XY: 0.105 AC XY: 7811 AN XY: 74408

African (AFR) AF: 0.0431 AC: 1788 AN: 41526

American (AMR) AF: 0.109 AC: 1664 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.0862 AC: 447 AN: 5188

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4820

European-Finnish (FIN) AF: 0.0900 AC: 953 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8675 AN: 67990

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.120 Hom.: 490

Bravo AF: 0.101

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.84
PhyloP100		0.45
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: rs2235676; hg19: chr6-24645697;