14-104179989-A-T

Variant names:

• chr14-104179989-A-T
• rs1547350
• NM_015656.2:c.*199A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015656.2(KIF26A):​c.*199A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 356,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: KIF26A NM_015656.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• 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):

• 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, Labcorp Genetics (formerly Invitae), Baylor College of Medicine Research Center

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*199A>T		3_prime_UTR	Exon 15 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.*199A>T		3_prime_UTR	Exon 15 of 15	ENSP00000388241.2	Q9ULI4
	KIF26A	ENST00000315264.7	TSL:1	c.*199A>T		3_prime_UTR	Exon 14 of 14	ENSP00000325452.7	C9JFF0
	KIF26A	ENST00000697132.1		c.*199A>T		3_prime_UTR	Exon 15 of 15	ENSP00000513129.1	A0A8V8TM02

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000112 AC: 4 AN: 356170 Hom.: 0 Cov.: 5 AF XY: 0.0000109 AC XY: 2 AN XY: 183482

African (AFR) AF: 0.00 AC: 0 AN: 9156

American (AMR) AF: 0.00 AC: 0 AN: 11014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11098

East Asian (EAS) AF: 0.00 AC: 0 AN: 24770

South Asian (SAS) AF: 0.00 AC: 0 AN: 19924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1644

European-Non Finnish (NFE) AF: 0.0000172 AC: 4 AN: 232502

Other (OTH) AF: 0.00 AC: 0 AN: 21346

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 37250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.73
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1547350;

hg19: chr14-104646326;