chr14-104139113-C-T

Variant names:

• chr14-104139113-C-T
• rs1468773229
• NM_015656.2:c.113C>T

Variant summary

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

The NM_015656.2(KIF26A):​c.113C>T​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF26A NM_015656.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.204
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30295056).

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.113C>T	p.Ala38Val	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.113C>T	p.Ala38Val	missense	Exon 2 of 15	ENSP00000388241.2	Q9ULI4
	KIF26A	ENST00000315264.7	TSL:1	c.-305C>T		5_prime_UTR	Exon 1 of 14	ENSP00000325452.7	C9JFF0
	KIF26A	ENST00000697132.1		c.209C>T	p.Ala70Val	missense	Exon 2 of 15	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 85878 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1329266 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 653742

African (AFR) AF: 0.00 AC: 0 AN: 26322

American (AMR) AF: 0.00 AC: 0 AN: 25022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23120

East Asian (EAS) AF: 0.00 AC: 0 AN: 29362

South Asian (SAS) AF: 0.00 AC: 0 AN: 70668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4038

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1049778

Other (OTH) AF: 0.00 AC: 0 AN: 54750

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.20
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.22
Sift	Benign	0.039	D
Sift4G	Benign	0.095	T
Polyphen		0.66	P
Vest4		0.097
MutPred		0.23		Gain of catalytic residue at A38 (P = 0.0817)
MVP		0.95
MPC		2.0
ClinPred		0.24	T
GERP RS		0.32
PromoterAI		-0.065	Neutral
Varity_R		0.050
gMVP		0.18
Mutation Taster		=96/4	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: rs1468773229; hg19: chr14-104605450;