rs2288751

chr2-240774012-T-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.1037+171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,112 control chromosomes in the GnomAD database, including 17,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17918 hom., cov: 33)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.539

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=-0.97).
• BP6: Variant 2-240774012-T-C is Benign according to our data. Variant chr2-240774012-T-C is described in ClinVar as [Benign]. Clinvar id is 682831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.1037+171A>G		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.1037+171A>G		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69366 AN: 151994 Hom.: 17894 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.427

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69426 AN: 152112 Hom.: 17918 Cov.: 33 AF XY: 0.452 AC XY: 33614 AN XY: 74356

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.422

Alfa AF: 0.407 Hom.: 2296

Bravo AF: 0.471

Asia WGS AF: 0.467 AC: 1627 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 19, 2018

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	-0.97
Cadd	Benign	6.5
Dann	Benign	0.83

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: rs2288751; hg19: chr2-241713429; COSMIC: COSV57481710; COSMIC: COSV57481710;