rs138964333

chr2-240723958-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001244008.2(KIF1A):c.4318+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,607,566 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0095 (79 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.355

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-240723958-G-A is Benign according to our data. Variant chr2-240723958-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240723958-G-A is described in Lovd as [Benign]. Variant chr2-240723958-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00687 (1046/152358) while in subpopulation NFE AF= 0.0118 (806/68030). AF 95% confidence interval is 0.0112. There are 4 homozygotes in gnomad4. There are 491 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.4318+17C>T		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.4318+17C>T		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152240 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00715 AC: 1774 AN: 248080 Hom.: 7 AF XY: 0.00722 AC XY: 974 AN XY: 134996

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.0165

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00346

Gnomad FIN exome AF: 0.00706

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.00565

GnomAD4 exome AF: 0.00953 AC: 13874 AN: 1455208 Hom.: 79 Cov.: 30 AF XY: 0.00951 AC XY: 6885 AN XY: 724294

Gnomad4 AFR exome AF: 0.00153

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00358

Gnomad4 FIN exome AF: 0.00721

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.00778

GnomAD4 genome AF: 0.00687 AC: 1046 AN: 152358 Hom.: 4 Cov.: 33 AF XY: 0.00659 AC XY: 491 AN XY: 74508

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00434

Gnomad4 FIN AF: 0.00696

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.0104 Hom.: 1

Bravo AF: 0.00638

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 09, 2023	- -

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.79
Dann	Benign	0.66

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: rs138964333; hg19: chr2-241663375;