2-240766810-C-T

Position:

• chr2-240766810-C-T

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.1684+105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 674,322 control chromosomes in the GnomAD database, including 12,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2207 hom., cov: 31)
  • Exomes 𝑓: 0.19 (9937 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.739

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=-0.89).
• BP6: Variant 2-240766810-C-T is Benign according to our data. Variant chr2-240766810-C-T is described in ClinVar as [Benign]. Clinvar id is 1288057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.1684+105G>A		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.1684+105G>A		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23228 AN: 149312 Hom.: 2203 Cov.: 31

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.186 AC: 97668 AN: 524894 Hom.: 9937 AF XY: 0.183 AC XY: 50343 AN XY: 275420

Gnomad4 AFR exome AF: 0.0540

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.0773

Gnomad4 SAS exome AF: 0.0942

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.156 AC: 23238 AN: 149428 Hom.: 2207 Cov.: 31 AF XY: 0.153 AC XY: 11155 AN XY: 72746

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0833

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.179

Alfa AF: 0.105 Hom.: 199

Bravo AF: 0.148

Asia WGS AF: 0.0810 AC: 282 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 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11681427; hg19: chr2-241706227; COSMIC: COSV57489047; COSMIC: COSV57489047;