6-24559052-C-G

Position:

• chr6-24559052-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014809.4(KIAA0319):​c.2695G>C​(p.Asp899His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3620429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2695G>C	p.Asp899His	missense_variant	17/21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2695G>C	p.Asp899His	missense_variant	17/21	1	NM_014809.4	ENSP00000367459.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2022

The c.2695G>C (p.D899H) alteration is located in exon 17 (coding exon 16) of the KIAA0319 gene. This alteration results from a G to C substitution at nucleotide position 2695, causing the aspartic acid (D) at amino acid position 899 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	.;.;.;.;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.36	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	.;.;M;.;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.9	.;D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	.;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		1.0, 1.0	.;.;.;D;D;D
Vest4		0.54
MutPred		0.31		.;.;Loss of ubiquitination at K904 (P = 0.0464);.;Loss of ubiquitination at K904 (P = 0.0464);Loss of ubiquitination at K904 (P = 0.0464);
MVP		0.45
MPC		0.41
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.55
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-24559280;