chr6-24559031-A-C

Variant names:

• chr6-24559031-A-C
• NM_014809.4:c.2716T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014809.4(KIAA0319):​c.2716T>G​(p.Leu906Val) 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. 13/22 in silico tools predict 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: 1.90
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27011216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319	NM_014809.4	c.2716T>G	p.Leu906Val	missense_variant	Exon 17 of 21	ENST00000378214.8	NP_055624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319	ENST00000378214.8	c.2716T>G	p.Leu906Val	missense_variant	Exon 17 of 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

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2716T>G (p.L906V) alteration is located in exon 17 (coding exon 16) of the KIAA0319 gene. This alteration results from a T to G substitution at nucleotide position 2716, causing the leucine (L) at amino acid position 906 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0020	.;.;.;.;T;T
Eigen	Benign	0.066
Eigen_PC	Benign	-0.0088
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D;D;D;D;.;D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	.;.;M;.;M;M
PhyloP100		1.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	.;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.040	.;D;T;D;D;D
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		1.0, 1.0	.;.;.;D;D;D
Vest4		0.44
MutPred		0.28		.;.;Gain of methylation at K904 (P = 0.0703);.;Gain of methylation at K904 (P = 0.0703);Gain of methylation at K904 (P = 0.0703);
MVP		0.27
MPC		0.39
ClinPred		0.97	D
GERP RS		0.45
Varity_R		0.17
gMVP		0.58
Mutation Taster		=80/20	polymorphism

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

hg19: chr6-24559259;