Genetic Variant KIF1A:p.Glu916_Glu917dup (chr2-240757423-A-ATCCTCC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001244008.2(KIF1A):c.2748_2753dupGGAGGA(p.Glu916_Glu917dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Publications

17 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 -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001244008.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.2748_2753dupGGAGGA	p.Glu916_Glu917dup	disruptive_inframe_insertion	Exon 27 of 49	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.2748_2753dupGGAGGA	p.Glu916_Glu917dup	disruptive_inframe_insertion	Exon 27 of 49	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.0000363

AC:

AN:

137556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000244

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000322

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1345186

Hom.:

Cov.:

AF XY:

0.0000528

AC XY:

AN XY:

663322

show subpopulations

African (AFR)

AF:

0.0000340

AC:

AN:

29382

American (AMR)

AF:

0.00

AC:

AN:

33864

Ashkenazi Jewish (ASJ)

AF:

0.0000418

AC:

AN:

23936

East Asian (EAS)

AF:

0.00

AC:

AN:

34166

South Asian (SAS)

AF:

0.0000932

AC:

AN:

75084

European-Finnish (FIN)

AF:

0.0000216

AC:

AN:

46352

Middle Eastern (MID)

AF:

0.000186

AC:

AN:

5376

European-Non Finnish (NFE)

AF:

0.0000528

AC:

AN:

1041190

Other (OTH)

AF:

0.0000358

AC:

AN:

55836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

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:

0.0000363

AC:

AN:

137556

Hom.:

Cov.:

AF XY:

0.0000601

AC XY:

AN XY:

66558

show subpopulations

African (AFR)

AF:

0.0000262

AC:

AN:

38136

American (AMR)

AF:

0.00

AC:

AN:

13388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3258

East Asian (EAS)

AF:

0.00

AC:

AN:

4660

South Asian (SAS)

AF:

0.000244

AC:

AN:

4096

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

8966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000322

AC:

AN:

62056

Other (OTH)

AF:

0.00

AC:

AN:

1888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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:

0.0000660

Hom.:

1564

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF1A: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-240757423-ATCCTCCTCCTCCTCCTCC-ATCCTCCTCCTCCTCCTCCTCCTCC

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