2-240789660-T-C

Position:

• chr2-240789660-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244008.2(KIF1A):​c.107-348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,070 control chromosomes in the GnomAD database, including 15,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15229 hom., cov: 33)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1A	NM_001244008.2	c.107-348A>G		intron_variant		ENST00000498729.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1A	ENST00000498729.9	c.107-348A>G		intron_variant		5	NM_001244008.2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63721 AN: 151952 Hom.: 15173 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.420 AC: 63822 AN: 152070 Hom.: 15229 Cov.: 33 AF XY: 0.418 AC XY: 31045 AN XY: 74346

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.375

Alfa AF: 0.380 Hom.: 1539

Bravo AF: 0.433

Asia WGS AF: 0.350 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.50

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: rs12989742; hg19: chr2-241729077;