Genetic Variant KIF26A:p.Pro268Leu (chr14-104157822-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015656.2(KIF26A):c.803C>T(p.Pro268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIF26A
NM_015656.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

Publications

0 publications found

Variant links:

Genes affected

KIF26A (HGNC:20226): (kinesin family member 26A) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in enteric nervous system development; negative regulation of signal transduction; and regulation of cell growth by extracellular stimulus. Predicted to be located in cytosol. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF26A Gene-Disease associations (from GenCC):

cortical dysplasia, complex, with other brain malformations 11
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Baylor College of Medicine Research Center

KIF26A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.104570866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF26A	NM_015656.2 link	c.803C>T	p.Pro268Leu	missense_variant	Exon 4 of 15	ENST00000423312.7	NP_056471.1	Q9ULI4
KIF26A	XM_011536641.3 link	c.-5+5361C>T		intron_variant	Intron 1 of 11		XP_011534943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF26A	ENST00000423312.7 link	c.803C>T	p.Pro268Leu	missense_variant	Exon 4 of 15	5	NM_015656.2	ENSP00000388241.2	Q9ULI4
KIF26A	ENST00000315264.7 link	c.386C>T	p.Pro129Leu	missense_variant	Exon 3 of 14	1		ENSP00000325452.7	C9JFF0
KIF26A	ENST00000697132.1 link	c.899C>T	p.Pro300Leu	missense_variant	Exon 4 of 15			ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457428

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110510

Other (OTH)

AF:

0.00

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 09, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.803C>T (p.P268L) alteration is located in exon 4 (coding exon 4) of the KIF26A gene. This alteration results from a C to T substitution at nucleotide position 803, causing the proline (P) at amino acid position 268 to be replaced by a leucine (L). 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

0.087

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.66

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.6

L;.

PhyloP100

-0.085

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.12

Sift

Benign

0.28

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0010

B;.

Vest4

0.23

MutPred

0.33

Loss of disorder (P = 0.0182);.;

MVP

0.40

MPC

0.11

ClinPred

0.057

GERP RS

1.9

Varity_R

0.057

gMVP

0.20

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over