14-104152042-G-A

Position:

• chr14-104152042-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015656.2(KIF26A):​c.316G>A​(p.Asp106Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF26A	NM_015656.2	c.316G>A	p.Asp106Asn	missense_variant	3/15	ENST00000423312.7	NP_056471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF26A	ENST00000423312.7	c.316G>A	p.Asp106Asn	missense_variant	3/15	5	NM_015656.2	ENSP00000388241.2
KIF26A	ENST00000315264	c.-102G>A		5_prime_UTR_variant	2/14	1		ENSP00000325452.7
KIF26A	ENST00000697132.1	c.412G>A	p.Asp138Asn	missense_variant	3/15			ENSP00000513129.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460398 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 20, 2021

The c.316G>A (p.D106N) alteration is located in exon 3 (coding exon 3) of the KIF26A gene. This alteration results from a G to A substitution at nucleotide position 316, causing the aspartic acid (D) at amino acid position 106 to be replaced by an asparagine (N). 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	0.23
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.8	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.42		Loss of ubiquitination at K107 (P = 0.0665);
MVP		0.91
MPC		0.32
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.37
gMVP		0.48

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: rs1566856106; hg19: chr14-104618379; COSMIC: COSV59464815;