17-5002851-GCCCC-GCCCCCCCCCCCCCCCCCCC

Variant names:

• chr17-5002851-G-GCCCCCCCCCCCCCCC
• rs10533622
• NM_006612.6:c.720+20_720+21insCCCCCCCCCCCCCCC

Variant summary

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

The NM_006612.6(KIF1C):​c.720+20_720+21insCCCCCCCCCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

Genes affected

KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

KIF1C Gene-Disease associations (from GenCC):

• spastic ataxia 2

  Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.720+20_720+21insCCCCCCCCCCCCCCC		intron_variant	Intron 8 of 22	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.720+20_720+21insCCCCCCCCCCCCCCC		intron_variant	Intron 9 of 23		XP_005256481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1C	ENST00000320785.10	c.720+9_720+10insCCCCCCCCCCCCCCC		intron_variant	Intron 8 of 22	1	NM_006612.6	ENSP00000320821.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1285162 Hom.: 0 Cov.: 0 AF XY: 0.00000156 AC XY: 1 AN XY: 642312

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31172

American (AMR) AF: 0.0000246 AC: 1 AN: 40728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23458

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36378

South Asian (SAS) AF: 0.00 AC: 0 AN: 77726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 971742

Other (OTH) AF: 0.00 AC: 0 AN: 53636

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs10533622; hg19: chr17-4906146;