17-5002851-GCCCC-GCCCCC

Variant names:

• chr17-5002851-G-GC
• rs10533622
• NM_006612.6:c.720+20dupC

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+20dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (16 hom., cov: 0)
  • Exomes 𝑓: 0.031 (6 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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-G-GC is Benign according to our data. Variant chr17-5002851-G-GC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 468859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00831 (1139/137006) while in subpopulation SAS AF = 0.0238 (97/4082). AF 95% confidence interval is 0.0199. There are 16 homozygotes in GnomAd4. There are 550 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6	c.720+20dupC		intron_variant	Intron 8 of 22	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3	c.720+20dupC		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+10insC		intron_variant	Intron 8 of 22	1	NM_006612.6	ENSP00000320821.5

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1138 AN: 136932 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.00257

Gnomad AMI AF: 0.00346

Gnomad AMR AF: 0.00846

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.00412

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00984

Gnomad OTH AF: 0.0136

GnomAD2 exomes AF: 0.0229 AC: 4426 AN: 193244 AF XY: 0.0235

Gnomad AFR exome AF: 0.00506

Gnomad AMR exome AF: 0.0363

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.0428

Gnomad FIN exome AF: 0.00201

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0237

GnomAD4 exome AF: 0.0312 AC: 39279 AN: 1257914 Hom.: 6 Cov.: 0 AF XY: 0.0331 AC XY: 20787 AN XY: 628022

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

African (AFR) AF: 0.00749 AC: 232 AN: 30966

American (AMR) AF: 0.0338 AC: 1339 AN: 39558

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 963 AN: 22836

East Asian (EAS) AF: 0.0368 AC: 1304 AN: 35468

South Asian (SAS) AF: 0.0876 AC: 6533 AN: 74594

European-Finnish (FIN) AF: 0.0149 AC: 678 AN: 45646

Middle Eastern (MID) AF: 0.0303 AC: 119 AN: 3924

European-Non Finnish (NFE) AF: 0.0278 AC: 26487 AN: 952456

Other (OTH) AF: 0.0310 AC: 1624 AN: 52466

⚠️ 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 AF: 0.00831 AC: 1139 AN: 137006 Hom.: 16 Cov.: 0 AF XY: 0.00835 AC XY: 550 AN XY: 65844

African (AFR) AF: 0.00262 AC: 95 AN: 36220

American (AMR) AF: 0.00845 AC: 114 AN: 13498

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 85 AN: 3310

East Asian (EAS) AF: 0.0113 AC: 51 AN: 4520

South Asian (SAS) AF: 0.0238 AC: 97 AN: 4082

European-Finnish (FIN) AF: 0.00412 AC: 34 AN: 8246

Middle Eastern (MID) AF: 0.0142 AC: 4 AN: 282

European-Non Finnish (NFE) AF: 0.00984 AC: 631 AN: 64118

Other (OTH) AF: 0.0134 AC: 25 AN: 1862

Alfa AF: 0.0202 Hom.: 580

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic ataxia 2 Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia Benign:1

Jan 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Sep 12, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;