NM_001244008.2:c.1684+17G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001244008.2(KIF1A):c.1684+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,568,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.14

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-240766898-C-T is Benign according to our data. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893. Variant chr2-240766898-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 445893.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.1684+17G>A		intron_variant	Intron 19 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.1684+17G>A		intron_variant	Intron 19 of 48	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000226

AC:

AN:

220850

AF XY:

0.0000250

show subpopulations

Gnomad AFR exome

AF:

0.000159

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1416486

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

704746

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32636

American (AMR)

AF:

0.00

AC:

AN:

41878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25520

East Asian (EAS)

AF:

0.00

AC:

AN:

38756

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1079422

Other (OTH)

AF:

0.0000679

AC:

AN:

58868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Jan 21, 2025

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

-0.86

CADD

Benign

0.73

(source)

DANN

Benign

0.55

PhyloP100

-2.1

Splicing

Name

Calibrated prediction

Score

Prediction

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