chr6-24545368-A-C

Variant names:

• chr6-24545368-A-C
• rs2817243
• NM_014809.4:c.*1797T>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.*1797T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,176 control chromosomes in the GnomAD database, including 694 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 0.080 (694 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: KIAA0319 NM_014809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 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.*1797T>G		3_prime_UTR	Exon 21 of 21	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.*1797T>G		3_prime_UTR	Exon 21 of 21	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.*1797T>G		3_prime_UTR	Exon 21 of 21	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.*1797T>G		3_prime_UTR	Exon 21 of 21	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.*1797T>G		3_prime_UTR	Exon 19 of 19	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.*1797T>G		3_prime_UTR	Exon 17 of 17	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12148 AN: 152054 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0735

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0799 AC: 12161 AN: 152172 Hom.: 694 Cov.: 32 AF XY: 0.0815 AC XY: 6060 AN XY: 74398

African (AFR) AF: 0.156 AC: 6455 AN: 41484

American (AMR) AF: 0.0542 AC: 828 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3466

East Asian (EAS) AF: 0.00946 AC: 49 AN: 5182

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10580

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0435 AC: 2961 AN: 68026

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0529 Hom.: 166

Bravo AF: 0.0778

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.047
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: rs2817243; hg19: chr6-24545596;