chr17-5002851-GCC-G

Variant names:

• chr17-5002850-CGC-CG
• rs10533622
• NM_006612.6:c.720+20delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006612.6(KIF1C):​c.720+20delC 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 0.038 (87 hom., cov: 0)
  • Exomes 𝑓: 0.12 (1071 hom.)
• Consequence: KIF1C NM_006612.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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 17-5002850-CGC-CG is Benign according to our data. Variant chr17-5002851-GC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1167058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1C	ENST00000320785.10	TSL:1 MANE Select	c.720+10delC		intron	N/A	ENSP00000320821.5	O43896
	KIF1C	ENST00000948910.1		c.720+10delC		intron	N/A	ENSP00000618969.1
	KIF1C	ENST00000948913.1		c.720+10delC		intron	N/A	ENSP00000618972.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5240 AN: 136808 Hom.: 87 Cov.: 0

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0876

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0327

Gnomad EAS AF: 0.00198

Gnomad SAS AF: 0.00901

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0563

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0353

GnomAD2 exomes AF: 0.183 AC: 35456 AN: 193244 AF XY: 0.189

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.115 AC: 137136 AN: 1188546 Hom.: 1071 Cov.: 0 AF XY: 0.118 AC XY: 69589 AN XY: 591930

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

African (AFR) AF: 0.0417 AC: 1260 AN: 30250

American (AMR) AF: 0.150 AC: 5412 AN: 36066

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2559 AN: 20958

East Asian (EAS) AF: 0.0907 AC: 2919 AN: 32170

South Asian (SAS) AF: 0.108 AC: 7293 AN: 67654

European-Finnish (FIN) AF: 0.112 AC: 4763 AN: 42674

Middle Eastern (MID) AF: 0.0791 AC: 299 AN: 3780

European-Non Finnish (NFE) AF: 0.118 AC: 107143 AN: 905558

Other (OTH) AF: 0.111 AC: 5488 AN: 49436

⚠️ 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: 0.0383 AC: 5236 AN: 136878 Hom.: 87 Cov.: 0 AF XY: 0.0358 AC XY: 2357 AN XY: 65786

African (AFR) AF: 0.0186 AC: 674 AN: 36216

American (AMR) AF: 0.0374 AC: 505 AN: 13502

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 108 AN: 3306

East Asian (EAS) AF: 0.00199 AC: 9 AN: 4524

South Asian (SAS) AF: 0.00906 AC: 37 AN: 4082

European-Finnish (FIN) AF: 0.0294 AC: 241 AN: 8206

Middle Eastern (MID) AF: 0.0461 AC: 13 AN: 282

European-Non Finnish (NFE) AF: 0.0548 AC: 3508 AN: 64034

Other (OTH) AF: 0.0350 AC: 65 AN: 1858

Alfa AF: 0.100 Hom.: 580

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Spastic ataxia 2 (1)

Computational scores

Source: dbNSFP v4.9

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

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10533622; hg19: chr17-4906145;