2-240787229-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001244008.2(KIF1A):c.429+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,601,840 control chromosomes in the GnomAD database, including 147,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19687 hom., cov: 34)

Exomes 𝑓: 0.42 ( 127948 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.305

Publications

7 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
hereditary spastic paraplegia 30
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-240787229-A-G is Benign according to our data. Variant chr2-240787229-A-G is described in ClinVar as Benign. ClinVar VariationId is 673387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 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.429+22T>C	intron	N/A	NP_001230937.1	Q12756-3
KIF1A	NM_001379631.1		c.429+22T>C	intron	N/A	NP_001366560.1
KIF1A	NM_001379642.1		c.429+22T>C	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.429+22T>C	intron	N/A	ENSP00000438388.1	Q12756-3
KIF1A	ENST00000675932.2		c.429+22T>C	intron	N/A	ENSP00000502786.2	A0A6Q8PHQ5
KIF1A	ENST00000675314.2		c.558+22T>C	intron	N/A	ENSP00000502584.2	A0A6Q8PH56

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74477

AN:

152008

Hom.:

19646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.413

AC:

102247

AN:

247550

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.415

AC:

602049

AN:

1449714

Hom.:

127948

Cov.:

AF XY:

0.410

AC XY:

296123

AN XY:

722016

show subpopulations

African (AFR)

AF:

0.715

AC:

23729

AN:

33210

American (AMR)

AF:

0.395

AC:

17633

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

8879

AN:

26032

East Asian (EAS)

AF:

0.468

AC:

18559

AN:

39616

South Asian (SAS)

AF:

0.289

AC:

24852

AN:

86008

European-Finnish (FIN)

AF:

0.386

AC:

20333

AN:

52676

Middle Eastern (MID)

AF:

0.376

AC:

2156

AN:

5734

European-Non Finnish (NFE)

AF:

0.418

AC:

460891

AN:

1101774

Other (OTH)

AF:

0.417

AC:

25017

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16279

32558

48837

65116

81395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14092

28184

42276

56368

70460

<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:

0.490

AC:

74544

AN:

152126

Hom.:

19687

Cov.:

AF XY:

0.482

AC XY:

35832

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.700

AC:

29065

AN:

41502

American (AMR)

AF:

0.435

AC:

6652

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1192

AN:

3470

East Asian (EAS)

AF:

0.446

AC:

2293

AN:

5144

South Asian (SAS)

AF:

0.280

AC:

1349

AN:

4818

European-Finnish (FIN)

AF:

0.372

AC:

3950

AN:

10610

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28649

AN:

67962

Other (OTH)

AF:

0.440

AC:

931

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1900

3800

5699

7599

9499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.440

Hom.:

2872

Bravo

AF:

0.507

Asia WGS

AF:

0.368

AC:

1284

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.35

PhyloP100

-0.30

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over