2-240757423-ATCCTCCTCCTCCTCCTCC-ATCCTCCTCCTCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

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

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 6.36

Publications

17 publications found

Variant links:

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]

KIF1A Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 9
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neuropathy, hereditary sensory, type 2C
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
hereditary spastic paraplegia 30
Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
PEHO syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary sensory and autonomic neuropathy type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 211282.

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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.2748_2753delGGAGGA	p.Glu916_Glu917del	disruptive_inframe_deletion	Exon 27 of 49	ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9 link	c.2748_2753delGGAGGA	p.Glu916_Glu917del	disruptive_inframe_deletion	Exon 27 of 49	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2021

AN:

137486

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0187

AC:

2065

AN:

110140

AF XY:

0.0190

show subpopulations

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 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

show subpopulations

African (AFR)

AF:

0.0274

AC:

616

AN:

22476

American (AMR)

AF:

0.00792

AC:

249

AN:

31420

Ashkenazi Jewish (ASJ)

AF:

0.0200

AC:

416

AN:

20780

East Asian (EAS)

AF:

0.00516

AC:

144

AN:

27932

South Asian (SAS)

AF:

0.00874

AC:

616

AN:

70482

European-Finnish (FIN)

AF:

0.00602

AC:

249

AN:

41376

Middle Eastern (MID)

AF:

0.00506

AC:

AN:

4936

European-Non Finnish (NFE)

AF:

0.0190

AC:

17994

AN:

948758

Other (OTH)

AF:

0.0158

AC:

790

AN:

49916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1060

2120

3179

4239

5299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.0147

AC:

2022

AN:

137566

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

941

AN XY:

66620

show subpopulations

African (AFR)

AF:

0.0181

AC:

690

AN:

38226

American (AMR)

AF:

0.00769

AC:

103

AN:

13396

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3258

East Asian (EAS)

AF:

0.00517

AC:

AN:

4646

South Asian (SAS)

AF:

0.00661

AC:

AN:

4082

European-Finnish (FIN)

AF:

0.00581

AC:

AN:

8954

Middle Eastern (MID)

AF:

0.00368

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0166

AC:

1029

AN:

62018

Other (OTH)

AF:

0.00948

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0467

Hom.:

1564

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign: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

- -

May 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

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.4

Mutation Taster

=165/35

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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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