chr2-240802560-C-T

Variant names:

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001244008.2(KIF1A):c.-60-4748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,010 control chromosomes in the GnomAD database, including 18,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 18986 hom., cov: 32)

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

3 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
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), G2P, Ambry Genetics, PanelApp Australia
hereditary spastic paraplegia 30
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
spastic paraplegia 30A, autosomal dominant
Inheritance: AR, AD Classification: STRONG Submitted by: PanelApp Australia
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

new If you want to explore the variant's impact on the transcript NM_001244008.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244008.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF1A	NM_001244008.2	MANE Select	c.-60-4748G>A	intron	N/A	NP_001230937.1	Q12756-3
KIF1A	NM_001379631.1		c.-60-4748G>A	intron	N/A	NP_001366560.1
KIF1A	NM_001379642.1		c.-60-4748G>A	intron	N/A	NP_001366571.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.-60-4748G>A	intron	N/A	ENSP00000438388.1	Q12756-3
KIF1A	ENST00000675932.2		c.-60-4748G>A	intron	N/A	ENSP00000502786.2	A0A6Q8PHQ5
KIF1A	ENST00000675314.2		c.-60-4748G>A	intron	N/A	ENSP00000502584.2	A0A6Q8PH56

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71703

AN:

151890

Hom.:

18939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.472

AC:

71797

AN:

152010

Hom.:

18986

Cov.:

AF XY:

0.471

AC XY:

34994

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.727

AC:

30144

AN:

41482

American (AMR)

AF:

0.389

AC:

5948

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1083

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2891

AN:

5178

South Asian (SAS)

AF:

0.367

AC:

1767

AN:

4816

European-Finnish (FIN)

AF:

0.403

AC:

4248

AN:

10538

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24409

AN:

67930

Other (OTH)

AF:

0.440

AC:

927

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1740

3480

5221

6961

8701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.384

Hom.:

15177

Bravo

AF:

0.481

Asia WGS

AF:

0.477

AC:

1665

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.097

(source)

DANN

Benign

0.35

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over