rs11688298

chr2-240763144-T-Achr2-240763144-T-Cchr2-240763144-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.59 (26823 hom., cov: 35)
  • Exomes 𝑓: 0.55 (224823 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.212

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: 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_single_submitter, 1 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	UniProt
KIF1A	NM_001244008.2	c.1949+22A>T		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.1949+22A>T		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89427 AN: 152056 Hom.: 26804 Cov.: 35

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

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.: 40 AF XY: 0.548 AC XY: 395186 AN XY: 721182

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.: 35 AF XY: 0.582 AC XY: 43327 AN XY: 74384

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

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

Other links and lift over

dbSNP: rs11688298; hg19: chr2-241702561; COSMIC: COSV57481653;