chr17-5002851-GCCC-G

Variant names:

• chr17-5002851-GCCC-G
• rs10533622
• NM_006612.6:c.720+18_720+20delCCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006612.6(KIF1C):​c.720+18_720+20delCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,421,838 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.04
• Publications: 1 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 17-5002851-GCCC-G is Benign according to our data. Variant chr17-5002851-GCCC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1344413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000394 (54/137096) while in subpopulation AFR AF = 0.000359 (13/36240). AF 95% confidence interval is 0.000219. There are 0 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	NM_006612.6	MANE Select	c.720+18_720+20delCCC		intron	N/A	NP_006603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.720+10_720+12delCCC		intron	N/A	ENSP00000320821.5

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 54 AN: 137022 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000741

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00206

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.00108

GnomAD2 exomes AF: 0.000440 AC: 85 AN: 193244 AF XY: 0.000466

Gnomad AFR exome AF: 0.000342

Gnomad AMR exome AF: 0.000236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.000425

Gnomad OTH exome AF: 0.000419

GnomAD4 exome AF: 0.000197 AC: 253 AN: 1284742 Hom.: 2 AF XY: 0.000195 AC XY: 125 AN XY: 642126

African (AFR) AF: 0.000321 AC: 10 AN: 31148

American (AMR) AF: 0.000147 AC: 6 AN: 40722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23450

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36372

South Asian (SAS) AF: 0.0000772 AC: 6 AN: 77724

European-Finnish (FIN) AF: 0.00151 AC: 70 AN: 46288

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

European-Non Finnish (NFE) AF: 0.000158 AC: 153 AN: 971420

Other (OTH) AF: 0.000131 AC: 7 AN: 53612

GnomAD4 genome AF: 0.000394 AC: 54 AN: 137096 Hom.: 0 Cov.: 0 AF XY: 0.000425 AC XY: 28 AN XY: 65898

African (AFR) AF: 0.000359 AC: 13 AN: 36240

American (AMR) AF: 0.0000739 AC: 1 AN: 13526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4526

South Asian (SAS) AF: 0.00 AC: 0 AN: 4086

European-Finnish (FIN) AF: 0.00206 AC: 17 AN: 8248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000327 AC: 21 AN: 64146

Other (OTH) AF: 0.00107 AC: 2 AN: 1862

Alfa AF: 0.000899 Hom.: 580

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic ataxia 2 Benign:1

Nov 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hereditary spastic paraplegia Benign:1

Apr 26, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	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: rs10533622; hg19: chr17-4906146;