Variant rs2288750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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. Variant chr2-240783028-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.864+16C>T		intron_variant		ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9 link	c.864+16C>T		intron_variant		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

GnomAD3 exomes

AF:

0.219

AC:

54419

AN:

248348

Hom.:

6842

AF XY:

0.207

AC XY:

27938

AN XY:

135020

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 SAS exome

AF:

0.106

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

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.272

AC:

41421

AN:

152124

Hom.:

6631

Cov.:

AF XY:

0.268

AC XY:

19904

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.444

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.202

Hom.:

4758

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 22, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.15

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over