rs10174559

Positions:

• chr2-240737359-G-A
• chr2-240737359-G-C

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.3902-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 531,326 control chromosomes in the GnomAD database, including 24,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (10637 hom., cov: 30)
  • Exomes 𝑓: 0.26 (13985 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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=-0.94).
• BP6: Variant 2-240737359-G-A is Benign according to our data. Variant chr2-240737359-G-A is described in ClinVar as [Benign]. Clinvar id is 1231571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.3902-191C>T		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.3902-191C>T		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51750 AN: 151742 Hom.: 10616 Cov.: 30

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.258 AC: 98041 AN: 379466 Hom.: 13985 Cov.: 2 AF XY: 0.253 AC XY: 50301 AN XY: 198796

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.341 AC: 51814 AN: 151860 Hom.: 10637 Cov.: 30 AF XY: 0.337 AC XY: 25009 AN XY: 74204

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.330

Alfa AF: 0.243 Hom.: 3785

Bravo AF: 0.362

Asia WGS AF: 0.290 AC: 1011 AN: 3478

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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.074
DANN	Benign	0.49

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: rs10174559; hg19: chr2-241676776;