14-104139094-C-G

Position:

• chr14-104139094-C-G

Variant summary

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

The NM_015656.2(KIF26A):​c.94C>G​(p.Pro32Ala) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.850

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]

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=0.33719224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26A	NM_015656.2	c.94C>G	p.Pro32Ala	missense_variant	2/15	ENST00000423312.7	NP_056471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26A	ENST00000423312.7	c.94C>G	p.Pro32Ala	missense_variant	2/15	5	NM_015656.2	ENSP00000388241.2
KIF26A	ENST00000315264	c.-324C>G		5_prime_UTR_variant	1/14	1		ENSP00000325452.7
KIF26A	ENST00000697132.1	c.190C>G	p.Pro64Ala	missense_variant	2/15			ENSP00000513129.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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

Aug 17, 2021

The c.94C>G (p.P32A) alteration is located in exon 2 (coding exon 2) of the KIF26A gene. This alteration results from a C to G substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by an alanine (A). 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	0.064
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Benign	0.20	T
Sift4G	Benign	0.21	T
Polyphen		0.84	P
Vest4		0.14
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.85
MPC		3.4
ClinPred		0.50	D
GERP RS		1.9
Varity_R		0.060
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs2037611709; hg19: chr14-104605431;