NM_015656.2:c.92C>T

Variant names:

• chr14-104139092-C-T
• rs952487027
• NM_015656.2:c.92C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_015656.2(KIF26A):​c.92C>T​(p.Ser31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. S31Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760
• 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 Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• cortical dysplasia, complex, with other brain malformations 11

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Baylor College of Medicine Research Center, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity KI26A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26410538).

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.92C>T	p.Ser31Phe	missense	Exon 2 of 15	NP_056471.1	Q9ULI4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26A	ENST00000423312.7	TSL:5 MANE Select	c.92C>T	p.Ser31Phe	missense	Exon 2 of 15	ENSP00000388241.2	Q9ULI4
	KIF26A	ENST00000315264.7	TSL:1	c.-326C>T		5_prime_UTR	Exon 1 of 14	ENSP00000325452.7	C9JFF0
	KIF26A	ENST00000697132.1		c.188C>T	p.Ser63Phe	missense	Exon 2 of 15	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000307 AC: 4 AN: 1302820 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 639956

African (AFR) AF: 0.00 AC: 0 AN: 25554

American (AMR) AF: 0.00 AC: 0 AN: 20058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22176

East Asian (EAS) AF: 0.00 AC: 0 AN: 28338

South Asian (SAS) AF: 0.00 AC: 0 AN: 66414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3884

European-Non Finnish (NFE) AF: 0.00000289 AC: 3 AN: 1038806

Other (OTH) AF: 0.0000186 AC: 1 AN: 53634

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.76
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.27		Loss of phosphorylation at S31 (P = 0.0123)
MVP		0.64
MPC		2.6
ClinPred		0.46	T
GERP RS		2.0
PromoterAI		0.0060	Neutral
Varity_R		0.13
gMVP		0.27
Mutation Taster		=90/10	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

dbSNP: rs952487027; hg19: chr14-104605429;