Genetic Variant KIAA0319:c.2734+3A>G (chr6-24559010-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_014809.4(KIAA0319):c.2734+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,608,892 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

KIAA0319
NM_014809.4 splice_region, intron

Scores

Splicing: ADA: 0.03965

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.66

Publications

0 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 6-24559010-T-C is Benign according to our data. Variant chr6-24559010-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3036021.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4 link	c.2734+3A>G		splice_region_variant, intron_variant	Intron 17 of 20	ENST00000378214.8	NP_055624.2	Q5VV43-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8 link	c.2734+3A>G		splice_region_variant, intron_variant	Intron 17 of 20	1	NM_014809.4	ENSP00000367459.3		Q5VV43-1

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000411

AC:

100

AN:

243294

AF XY:

0.000511

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.000473

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000380

AC:

554

AN:

1456516

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

302

AN XY:

723964

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33428

American (AMR)

AF:

0.000319

AC:

AN:

43920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.000823

AC:

AN:

85034

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53192

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.000388

AC:

431

AN:

1109844

Other (OTH)

AF:

0.000233

AC:

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000328

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000351

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KIAA0319-related disorder

Benign:1

Dec 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.7

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.040

dbscSNV1_RF

Benign

0.22

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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6-24559010-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over