rs2288750

chr2-240783028-G-Achr2-240783028-G-Cchr2-240783028-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.763

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=-0.91).
• 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	UniProt
KIF1A	NM_001244008.2	c.864+16C>T		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.864+16C>T		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41401 AN: 152006 Hom.: 6623 Cov.: 34

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

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.: 31 AF XY: 0.200 AC XY: 144972 AN XY: 723286

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.: 34 AF XY: 0.268 AC XY: 19904 AN XY: 74368

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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	-0.91
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

Other links and lift over

dbSNP: rs2288750; hg19: chr2-241722445;