2-240737055-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001244008.2(KIF1A):c.4007+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000779 in 1,604,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 splice_region, intron

Scores

Splicing: ADA: 0.00003139

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.341

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

KIF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-240737055-C-T is Benign according to our data. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-240737055-C-T is described in CliVar as Likely_benign. Clinvar id is 464242.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.4007+8G>A		splice_region_variant, intron_variant	Intron 38 of 48	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.4007+8G>A		splice_region_variant, intron_variant	Intron 38 of 48	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000100

AC:

AN:

249108

AF XY:

0.0000888

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000805

AC:

117

AN:

1452720

Hom.:

Cov.:

AF XY:

0.0000789

AC XY:

AN XY:

722710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33280

American (AMR)

AF:

0.000381

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000879

AC:

AN:

1103948

Other (OTH)

AF:

0.0000333

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000526

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41430

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.0000491

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KIF1A-related disorder

Benign:1

Mar 24, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9

Benign:1

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.84

CADD

Benign

3.5

(source)

DANN

Benign

0.47

PhyloP100

-0.34

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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