Variant 2-240763144-T-A 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.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

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:

KIF1A (HGNC:):

KIF1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). 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. Variant chr2-240763144-T-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
KIF1A	NM_001244008.2 linkuse as main transcript	c.1949+22A>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 linkuse as main transcript	c.1949+22A>T		intron_variant		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

GnomAD3 exomes

AF:

0.531

AC:

125788

AN:

236736

Hom.:

34477

AF XY:

0.526

AC XY:

68084

AN XY:

129380

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 SAS exome

AF:

0.407

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

Gnomad4 AFR exome

AF:

0.702

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.668

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.588

AC:

89479

AN:

152174

Hom.:

26823

Cov.:

AF XY:

0.582

AC XY:

43327

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.508

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.581

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.88

DANN

Benign

0.68

BranchPoint Hunter

0.0

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