2-240757423-ATCCTCCTCCTCCTCCTCC-ATCCTCCTCCTCC

Variant names:

• chr2-240757423-ATCCTCC-A
• rs10594016
• NM_001244008.2:c.2748_2753delGGAGGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_001244008.2(KIF1A):​c.2748_2753delGGAGGA​(p.Glu916_Glu917del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0171 in 1,355,642 control chromosomes in the GnomAD database, including 153 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.015 (17 hom., cov: 0)
  • Exomes 𝑓: 0.017 (136 hom.)
• Consequence: KIF1A NM_001244008.2 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:6
• Conservation: PhyloP100: 6.36

Genes affected

KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001244008.2
• BP6: Variant 2-240757423-ATCCTCC-A is Benign according to our data. Variant chr2-240757423-ATCCTCC-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211282.We mark this variant Likely_benign, oryginal submissions are: {Benign=6, Uncertain_significance=1}. Variant chr2-240757423-ATCCTCC-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2022/137566) while in subpopulation AFR AF= 0.0181 (690/38226). AF 95% confidence interval is 0.0169. There are 17 homozygotes in gnomad4. There are 941 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.2748_2753delGGAGGA	p.Glu916_Glu917del	disruptive_inframe_deletion	Exon 27 of 49	ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.2748_2753delGGAGGA	p.Glu916_Glu917del	disruptive_inframe_deletion	Exon 27 of 49	5	NM_001244008.2	ENSP00000438388.1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2021 AN: 137486 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.00770

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00536

Gnomad SAS AF: 0.00659

Gnomad FIN AF: 0.00581

Gnomad MID AF: 0.00342

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.00954

GnomAD3 exomes AF: 0.0187 AC: 2065 AN: 110140 Hom.: 11 AF XY: 0.0190 AC XY: 1132 AN XY: 59702

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.0274

Gnomad EAS exome AF: 0.0102

Gnomad SAS exome AF: 0.0140

Gnomad FIN exome AF: 0.00898

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0177

GnomAD4 exome AF: 0.0173 AC: 21099 AN: 1218076 Hom.: 136 AF XY: 0.0171 AC XY: 10284 AN XY: 600892

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.00792

Gnomad4 ASJ exome AF: 0.0200

Gnomad4 EAS exome AF: 0.00516

Gnomad4 SAS exome AF: 0.00874

Gnomad4 FIN exome AF: 0.00602

Gnomad4 NFE exome AF: 0.0190

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0147 AC: 2022 AN: 137566 Hom.: 17 Cov.: 0 AF XY: 0.0141 AC XY: 941 AN XY: 66620

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.00769

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.00517

Gnomad4 SAS AF: 0.00661

Gnomad4 FIN AF: 0.00581

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.00948

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:6

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1 Benign:2

Jun 27, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 29, 2023

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

Oct 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KIF1A: BS1, BS2 -

Intellectual disability, autosomal dominant 9 Benign:1

Dec 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10594016; hg19: chr2-241696840;