6-24645382-A-G

Variant names:

• chr6-24645382-A-G
• rs2235677
• NM_014809.4:c.-106+354T>C

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+354T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,086 control chromosomes in the GnomAD database, including 38,150 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 0.70 (38150 hom., cov: 32)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.-106+354T>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.-106+245T>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.-106+653T>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.-106+354T>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.-106+354T>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000901508.1		c.-106+653T>C		intron	N/A	ENSP00000571567.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106837 AN: 151968 Hom.: 38122 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.703 AC: 106916 AN: 152086 Hom.: 38150 Cov.: 32 AF XY: 0.699 AC XY: 51979 AN XY: 74314

African (AFR) AF: 0.796 AC: 33017 AN: 41494

American (AMR) AF: 0.767 AC: 11718 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2163 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4519 AN: 5174

South Asian (SAS) AF: 0.696 AC: 3356 AN: 4820

European-Finnish (FIN) AF: 0.538 AC: 5673 AN: 10544

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 44011 AN: 67988

Other (OTH) AF: 0.712 AC: 1503 AN: 2110

Alfa AF: 0.675 Hom.: 4502

Bravo AF: 0.724

Asia WGS AF: 0.792 AC: 2754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.87
PhyloP100		-0.34
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: rs2235677; hg19: chr6-24645610;