14-104138742-C-G

Variant names:

• chr14-104138742-C-G
• rs912719457
• NM_015656.2:c.20C>G

Variant summary

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

The NM_015656.2(KIF26A):​c.20C>G​(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000895 in 1,117,190 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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-DT (HGNC:55439): (KIF26A divergent transcript)

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=0.3182421).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015656.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26A	NM_015656.2	MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 15	NP_056471.1	Q9ULI4
	KIF26A-DT	NR_158217.1		n.-113G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 15	ENSP00000388241.2	Q9ULI4
	KIF26A	ENST00000926957.1		c.20C>G	p.Pro7Arg	missense	Exon 1 of 15	ENSP00000597016.1
	KIF26A	ENST00000697132.1		c.139-301C>G		intron	N/A	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.95e-7 AC: 1 AN: 1117190 Hom.: 0 Cov.: 30 AF XY: 0.00000187 AC XY: 1 AN XY: 534094

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22786

American (AMR) AF: 0.00 AC: 0 AN: 8722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14750

East Asian (EAS) AF: 0.00 AC: 0 AN: 26210

South Asian (SAS) AF: 0.0000321 AC: 1 AN: 31176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3016

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 941814

Other (OTH) AF: 0.00 AC: 0 AN: 44858

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.91
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.20	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.21
Sift	Benign	0.034	D
Sift4G	Benign	0.84	T
Polyphen		0.77	P
Vest4		0.080
MutPred		0.38		Gain of MoRF binding (P = 2e-04)
MVP		0.86
MPC		2.1
ClinPred		0.17	T
GERP RS		2.2
PromoterAI		0.039	Neutral
Varity_R		0.058
gMVP		0.19
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs912719457; hg19: chr14-104605079;