2-240723958-G-A
Variant names:
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.4318+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,607,566 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0095 ( 79 hom. )
Consequence
KIF1A
NM_001244008.2 intron
NM_001244008.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.355
Publications
2 publications found
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 9Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- syndromic intellectual disabilityInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- neuropathy, hereditary sensory, type 2CInheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- hereditary spastic paraplegia 30Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
- autosomal dominant non-syndromic intellectual disabilityInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- PEHO syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary sensory and autonomic neuropathy type 2Inheritance: 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=-0.86).
BP6
Variant 2-240723958-G-A is Benign according to our data. Variant chr2-240723958-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00687 (1046/152358) while in subpopulation NFE AF = 0.0118 (806/68030). AF 95% confidence interval is 0.0112. There are 4 homozygotes in GnomAd4. There are 491 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 4 AR,AD gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00687 AC: 1046AN: 152240Hom.: 4 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1046
AN:
152240
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00715 AC: 1774AN: 248080 AF XY: 0.00722 show subpopulations
GnomAD2 exomes
AF:
AC:
1774
AN:
248080
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00953 AC: 13874AN: 1455208Hom.: 79 Cov.: 30 AF XY: 0.00951 AC XY: 6885AN XY: 724294 show subpopulations
GnomAD4 exome
AF:
AC:
13874
AN:
1455208
Hom.:
Cov.:
30
AF XY:
AC XY:
6885
AN XY:
724294
show subpopulations
African (AFR)
AF:
AC:
51
AN:
33402
American (AMR)
AF:
AC:
61
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
432
AN:
26104
East Asian (EAS)
AF:
AC:
3
AN:
39666
South Asian (SAS)
AF:
AC:
308
AN:
86148
European-Finnish (FIN)
AF:
AC:
376
AN:
52122
Middle Eastern (MID)
AF:
AC:
3
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
12172
AN:
1107136
Other (OTH)
AF:
AC:
468
AN:
60178
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.460
Heterozygous variant carriers
0
639
1279
1918
2558
3197
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00687 AC: 1046AN: 152358Hom.: 4 Cov.: 33 AF XY: 0.00659 AC XY: 491AN XY: 74508 show subpopulations
GnomAD4 genome
AF:
AC:
1046
AN:
152358
Hom.:
Cov.:
33
AF XY:
AC XY:
491
AN XY:
74508
show subpopulations
African (AFR)
AF:
AC:
59
AN:
41584
American (AMR)
AF:
AC:
24
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
AC:
47
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
21
AN:
4834
European-Finnish (FIN)
AF:
AC:
74
AN:
10628
Middle Eastern (MID)
AF:
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
AC:
806
AN:
68030
Other (OTH)
AF:
AC:
12
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
59
119
178
238
297
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Jun 26, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
May 01, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
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
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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