NM_001244008.2:c.1421+9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001244008.2(KIF1A):​c.1421+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,610,984 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 10 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.43

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 2-240769618-G-A is Benign according to our data. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240769618-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 513030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000131 (20/152282) while in subpopulation SAS AF = 0.00311 (15/4822). AF 95% confidence interval is 0.00192. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 10 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1ANM_001244008.2 linkc.1421+9C>T intron_variant Intron 16 of 48 ENST00000498729.9 NP_001230937.1 Q12756-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1AENST00000498729.9 linkc.1421+9C>T intron_variant Intron 16 of 48 5 NM_001244008.2 ENSP00000438388.1 Q12756-3

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00311
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000433
AC:
106
AN:
244920
AF XY:
0.000623
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000364
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.000218
AC:
318
AN:
1458702
Hom.:
10
Cov.:
31
AF XY:
0.000314
AC XY:
228
AN XY:
725584
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33440
American (AMR)
AF:
0.0000224
AC:
1
AN:
44592
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26086
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39678
South Asian (SAS)
AF:
0.00322
AC:
277
AN:
86096
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52644
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
0.0000252
AC:
28
AN:
1110144
Other (OTH)
AF:
0.000149
AC:
9
AN:
60284
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
13
26
38
51
64
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.000131
AC:
20
AN:
152282
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.0000481
AC:
2
AN:
41564
American (AMR)
AF:
0.000131
AC:
2
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00311
AC:
15
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.533
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000494
Hom.:
0
Bravo
AF:
0.0000340
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 02, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.0040
DANN
Benign
0.44
PhyloP100
-1.4
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs372601809; hg19: chr2-241709035; API