rs11688298

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1949+22A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,602,658 control chromosomes in the GnomAD database, including 251,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.59 ( 26823 hom., cov: 35)

Exomes 𝑓: 0.55 ( 224823 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.212

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: 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: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-240763144-T-A is Benign according to our data. Variant chr2-240763144-T-A is described in ClinVar as [Benign]. Clinvar id is 671033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.1949+22A>T		intron_variant	Intron 21 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.1949+22A>T		intron_variant	Intron 21 of 48	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89427

AN:

152056

Hom.:

26804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.587

GnomAD2 exomes

AF:

0.531

AC:

125788

AN:

236736

AF XY:

0.526

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.553

AC:

802423

AN:

1450484

Hom.:

224823

Cov.:

AF XY:

0.548

AC XY:

395186

AN XY:

721182

show subpopulations

African (AFR)

AF:

0.702

AC:

23435

AN:

33376

American (AMR)

AF:

0.410

AC:

18138

AN:

44220

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

15552

AN:

25970

East Asian (EAS)

AF:

0.668

AC:

26396

AN:

39494

South Asian (SAS)

AF:

0.404

AC:

34583

AN:

85538

European-Finnish (FIN)

AF:

0.523

AC:

24808

AN:

47446

Middle Eastern (MID)

AF:

0.549

AC:

3104

AN:

5656

European-Non Finnish (NFE)

AF:

0.562

AC:

622632

AN:

1108730

Other (OTH)

AF:

0.562

AC:

33775

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

19537

39073

58610

78146

97683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.588

AC:

89479

AN:

152174

Hom.:

26823

Cov.:

AF XY:

0.582

AC XY:

43327

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.690

AC:

28669

AN:

41528

American (AMR)

AF:

0.514

AC:

7861

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2108

AN:

3468

East Asian (EAS)

AF:

0.680

AC:

3512

AN:

5166

South Asian (SAS)

AF:

0.420

AC:

2031

AN:

4830

European-Finnish (FIN)

AF:

0.508

AC:

5381

AN:

10596

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37895

AN:

67964

Other (OTH)

AF:

0.581

AC:

1230

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1974

3948

5923

7897

9871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.568

Hom.:

4605

Bravo

AF:

0.594

Asia WGS

AF:

0.536

AC:

1865

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.88

(source)

DANN

Benign

0.68

PhyloP100

-0.21

BranchPoint Hunter

0.0

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

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.

rs11688298

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