17-5002851-GCCCC-GC

Position:

• chr17-5002851-GCCCC-GC

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006612.6(KIF1C):​c.720+18_720+20del 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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 17-5002851-GCCC-G is Benign according to our data. Variant chr17-5002851-GCCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1344413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1C	NM_006612.6	c.720+18_720+20del		intron_variant		ENST00000320785.10
KIF1C	XM_005256424.3	c.720+18_720+20del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1C	ENST00000320785.10	c.720+18_720+20del		intron_variant		1	NM_006612.6	P1

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

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

Gnomad4 AFR exome AF: 0.000321

Gnomad4 AMR exome AF: 0.000147

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000275

Gnomad4 SAS exome AF: 0.0000772

Gnomad4 FIN exome AF: 0.00151

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000131

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

Gnomad4 AFR AF: 0.000359

Gnomad4 AMR AF: 0.0000739

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00206

Gnomad4 NFE AF: 0.000327

Gnomad4 OTH AF: 0.00107

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Hereditary spastic paraplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs10533622; hg19: chr17-4906146;