Genetic Variant KIF1C:c.720+18_720+20delCCC (chr17-5002851-GCCC-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.04

Publications

1 publications found

Variant links:

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

KIF1C links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1C	NM_006612.6 link	c.720+18_720+20delCCC		intron_variant	Intron 8 of 22	ENST00000320785.10	NP_006603.2
KIF1C	XM_005256424.3 link	c.720+18_720+20delCCC		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 link	c.720+10_720+12delCCC		intron_variant	Intron 8 of 22	1	NM_006612.6	ENSP00000320821.5

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

137022

Hom.:

Cov.:

show subpopulations

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:

AN:

193244

AF XY:

0.000466

show subpopulations

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.:

AF XY:

0.000195

AC XY:

125

AN XY:

642126

show subpopulations

African (AFR)

AF:

0.000321

AC:

AN:

31148

American (AMR)

AF:

0.000147

AC:

AN:

40722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23450

East Asian (EAS)

AF:

0.0000275

AC:

AN:

36372

South Asian (SAS)

AF:

0.0000772

AC:

AN:

77724

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

46288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4006

European-Non Finnish (NFE)

AF:

0.000158

AC:

153

AN:

971420

Other (OTH)

AF:

0.000131

AC:

AN:

53612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000394

AC:

AN:

137096

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

AN XY:

65898

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

36240

American (AMR)

AF:

0.0000739

AC:

AN:

13526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

4526

South Asian (SAS)

AF:

0.00

AC:

AN:

4086

European-Finnish (FIN)

AF:

0.00206

AC:

AN:

8248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000327

AC:

AN:

64146

Other (OTH)

AF:

0.00107

AC:

AN:

1862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.629

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000899

Hom.:

580

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism

(source)

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

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17-5002851-GCCCC-GC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over