1-245688693-GAC-CAT

Variant names:

• chr1-245688693-GAC-CAT
• NM_018012.4:c.5710_5712delGACinsCAT
• KIF26B p.Asp1904His

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_018012.4(KIF26B):​c.5710_5712delGACinsCAT​(p.Asp1904His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. D1904N) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF26B NM_018012.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.79
• Publications: 0 publications found

Genes affected

KIF26B (HGNC:25484): (kinesin family member 26B) The protein encoded by this gene is an intracellular motor protein thought to transport organelles along microtubules. The encoded protein is required for kidney development. Elevated levels of this protein have been found in some breast and colorectal cancers. [provided by RefSeq, Mar 2017]

LOC105373265 (HGNC:):

ACMG classification

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

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-245688693-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 446270.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018012.4. 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
	KIF26B	NM_018012.4	MANE Select	c.5710_5712delGACinsCAT	p.Asp1904His	missense	N/A	NP_060482.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF26B	ENST00000407071.7	TSL:1 MANE Select	c.5710_5712delGACinsCAT	p.Asp1904His	missense	N/A	ENSP00000385545.2	Q2KJY2-1
	KIF26B	ENST00000366518.4	TSL:5	c.4567_4569delGACinsCAT	p.Asp1523His	missense	N/A	ENSP00000355475.4	B7WPD9

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.8

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

hg19: chr1-245851995;