2-240789426-C-T

Variant names:

• chr2-240789426-C-T
• rs2288745
• NM_001244008.2:c.107-114G>A

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.107-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 828,034 control chromosomes in the GnomAD database, including 43,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9578 hom., cov: 32)
  • Exomes 𝑓: 0.31 (34417 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.226

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=-0.83).
• BP6: Variant 2-240789426-C-T is Benign according to our data. Variant chr2-240789426-C-T is described in ClinVar as [Benign]. Clinvar id is 682826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.107-114G>A		intron_variant	Intron 2 of 48	ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.107-114G>A		intron_variant	Intron 2 of 48	5	NM_001244008.2	ENSP00000438388.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53198 AN: 151868 Hom.: 9564 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.313 AC: 211530 AN: 676048 Hom.: 34417 AF XY: 0.309 AC XY: 109421 AN XY: 354152

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.350 AC: 53229 AN: 151986 Hom.: 9578 Cov.: 32 AF XY: 0.350 AC XY: 25990 AN XY: 74274

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.323

Alfa AF: 0.336 Hom.: 1098

Bravo AF: 0.350

Asia WGS AF: 0.320 AC: 1118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.83
CADD	Benign	7.5
DANN	Benign	0.37

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: rs2288745; hg19: chr2-241728843; COSMIC: COSV57496743; COSMIC: COSV57496743;