chr14-104172104-A-G

Variant names:

• chr14-104172104-A-G
• rs947001
• NM_015656.2:c.1326+169A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015656.2(KIF26A):​c.1326+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,262 control chromosomes in the GnomAD database, including 46,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46687 hom., cov: 36)
• Consequence: KIF26A NM_015656.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 9 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):

• cortical dysplasia, complex, with other brain malformations 11

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF26A	NM_015656.2	c.1326+169A>G		intron_variant	Intron 6 of 14	ENST00000423312.7	NP_056471.1
KIF26A	XM_011536641.3	c.399+169A>G		intron_variant	Intron 3 of 11		XP_011534943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF26A	ENST00000423312.7	c.1326+169A>G		intron_variant	Intron 6 of 14	5	NM_015656.2	ENSP00000388241.2
KIF26A	ENST00000315264.7	c.909+169A>G		intron_variant	Intron 5 of 13	1		ENSP00000325452.7
KIF26A	ENST00000697132.1	c.1422+169A>G		intron_variant	Intron 6 of 14			ENSP00000513129.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118034 AN: 152144 Hom.: 46631 Cov.: 36

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.776 AC: 118149 AN: 152262 Hom.: 46687 Cov.: 36 AF XY: 0.778 AC XY: 57936 AN XY: 74426

African (AFR) AF: 0.943 AC: 39210 AN: 41584

American (AMR) AF: 0.712 AC: 10895 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2784 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4031 AN: 5164

South Asian (SAS) AF: 0.776 AC: 3749 AN: 4830

European-Finnish (FIN) AF: 0.759 AC: 8039 AN: 10598

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47031 AN: 67996

Other (OTH) AF: 0.762 AC: 1612 AN: 2116

Alfa AF: 0.737 Hom.: 5186

Bravo AF: 0.781

Asia WGS AF: 0.805 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.099
DANN	Benign	0.17
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs947001; hg19: chr14-104638441;