rs2038137

Positions:

• chr6-24645715-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168375.2(KIAA0319):​c.-194A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,480 control chromosomes in the GnomAD database, including 36,696 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 0.69 (36623 hom., cov: 29)
  • Exomes 𝑓: 0.62 (73 hom.)
• Consequence: KIAA0319 NM_001168375.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.-106+21A>C		intron_variant		ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.-106+21A>C		intron_variant		1	NM_014809.4	ENSP00000367459.3
KIAA0319	ENST00000537886.5	c.-106+21A>C		intron_variant		1		ENSP00000439700.1
KIAA0319	ENST00000430948.6	c.-169A>C		5_prime_UTR_variant	1/20	2		ENSP00000401086.2
KIAA0319	ENST00000535378.5	c.-224+21A>C		intron_variant		2		ENSP00000442403.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104159 AN: 150996 Hom.: 36596 Cov.: 29

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.699

GnomAD4 exome AF: 0.618 AC: 225 AN: 364 Hom.: 73 Cov.: 0 AF XY: 0.613 AC XY: 125 AN XY: 204

Gnomad4 AFR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.690 AC: 104238 AN: 151116 Hom.: 36623 Cov.: 29 AF XY: 0.686 AC XY: 50601 AN XY: 73780

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.704

Alfa AF: 0.652 Hom.: 4122

Bravo AF: 0.715

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2038137; hg19: chr6-24645943;