Genetic Variant KIAA0319:c.1280-9_1280-8dupTT (chr6-24579957-C-CAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014809.4(KIAA0319):c.1280-9_1280-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000907 in 1,566,230 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

KIAA0319
NM_014809.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.568

Publications

4 publications found

Variant links:

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]

KIAA0319 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA0319	NM_014809.4	MANE Select	c.1280-9_1280-8dupTT	splice_region intron	N/A	NP_055624.2	Q5VV43-1
KIAA0319	NM_001168375.2		c.1280-9_1280-8dupTT	splice_region intron	N/A	NP_001161847.1	Q5VV43-1
KIAA0319	NM_001350403.2		c.1280-9_1280-8dupTT	splice_region intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1280-8_1280-7insTT	splice_region intron	N/A	ENSP00000367459.3	Q5VV43-1
KIAA0319	ENST00000537886.5	TSL:1	c.1280-8_1280-7insTT	splice_region intron	N/A	ENSP00000439700.1	Q5VV43-4
KIAA0319	ENST00000616673.4	TSL:1	c.-449-8_-449-7insTT	splice_region intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000984

AC:

AN:

182878

AF XY:

0.0000924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000976

AC:

138

AN:

1414550

Hom.:

Cov.:

AF XY:

0.0000870

AC XY:

AN XY:

700794

show subpopulations

African (AFR)

AF:

0.0000313

AC:

AN:

31956

American (AMR)

AF:

0.000104

AC:

AN:

38444

Ashkenazi Jewish (ASJ)

AF:

0.0000396

AC:

AN:

25246

East Asian (EAS)

AF:

0.000107

AC:

AN:

37252

South Asian (SAS)

AF:

0.0000248

AC:

AN:

80728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.0000976

AC:

106

AN:

1085696

Other (OTH)

AF:

0.000342

AC:

AN:

58480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151680

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000194

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67864

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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6-24579957-CAA-CAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over