2-240783028-G-A

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.864+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,604,656 control chromosomes in the GnomAD database, including 39,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6631 hom., cov: 34)

Exomes 𝑓: 0.21 ( 33223 hom. )

Consequence

KIF1A
NM_001244008.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.763

Publications

9 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

Computational evidence support a benign effect (REVEL=0.014).

BP6

Variant 2-240783028-G-A is Benign according to our data. Variant chr2-240783028-G-A is described in ClinVar as [Benign]. Clinvar id is 283505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.864+16C>T		intron_variant	Intron 9 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.864+16C>T		intron_variant	Intron 9 of 48	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41401

AN:

152006

Hom.:

6623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.245

GnomAD2 exomes

AF:

0.219

AC:

54419

AN:

248348

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.443

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.205

AC:

297905

AN:

1452532

Hom.:

33223

Cov.:

AF XY:

0.200

AC XY:

144972

AN XY:

723286

show subpopulations

African (AFR)

AF:

0.454

AC:

15088

AN:

33268

American (AMR)

AF:

0.267

AC:

11934

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

5147

AN:

26082

East Asian (EAS)

AF:

0.374

AC:

14809

AN:

39634

South Asian (SAS)

AF:

0.107

AC:

9236

AN:

86102

European-Finnish (FIN)

AF:

0.171

AC:

9035

AN:

52972

Middle Eastern (MID)

AF:

0.206

AC:

1187

AN:

5754

European-Non Finnish (NFE)

AF:

0.198

AC:

218513

AN:

1103902

Other (OTH)

AF:

0.216

AC:

12956

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

10700

21399

32099

42798

53498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.272

AC:

41421

AN:

152124

Hom.:

6631

Cov.:

AF XY:

0.268

AC XY:

19904

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.444

AC:

18442

AN:

41490

American (AMR)

AF:

0.271

AC:

4146

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

721

AN:

3470

East Asian (EAS)

AF:

0.339

AC:

1744

AN:

5152

South Asian (SAS)

AF:

0.107

AC:

514

AN:

4812

European-Finnish (FIN)

AF:

0.159

AC:

1688

AN:

10616

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13451

AN:

67976

Other (OTH)

AF:

0.242

AC:

512

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1471

2943

4414

5886

7357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.209

Hom.:

7424

Bravo

AF:

0.290

Asia WGS

AF:

0.218

AC:

760

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Sep 22, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.91

CADD

Benign

0.15

(source)

DANN

Benign

0.67

PhyloP100

-0.76

PromoterAI

0.033

Neutral

(source)

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

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2-240783028-G-A

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