chr2-240788042-G-C

Position:

• chr2-240788042-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001244008.2(KIF1A):​c.363+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.16 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.03

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]

KIF1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-240788042-G-C is Benign according to our data. Variant chr2-240788042-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 701810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1A	NM_001244008.2	c.363+9C>G		intron_variant		ENST00000498729.9	NP_001230937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9	c.363+9C>G		intron_variant		5	NM_001244008.2	ENSP00000438388.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 135 AN: 107706 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000345

Gnomad EAS AF: 0.00220

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.00343

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000895

Gnomad OTH AF: 0.000684

GnomAD3 exomes AF: 0.0565 AC: 5851 AN: 103482 Hom.: 0 AF XY: 0.0509 AC XY: 2868 AN XY: 56354

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.0787

Gnomad EAS exome AF: 0.0743

Gnomad SAS exome AF: 0.0356

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0278

Gnomad OTH exome AF: 0.0989

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.155 AC: 60139 AN: 387228 Hom.: 4 Cov.: 18 AF XY: 0.152 AC XY: 29710 AN XY: 195854

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0908

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0670

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00126 AC: 136 AN: 107786 Hom.: 0 Cov.: 30 AF XY: 0.00165 AC XY: 84 AN XY: 50772

Gnomad4 AFR AF: 0.00139

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.000345

Gnomad4 EAS AF: 0.00220

Gnomad4 SAS AF: 0.00231

Gnomad4 FIN AF: 0.00343

Gnomad4 NFE AF: 0.000895

Gnomad4 OTH AF: 0.000678

Alfa AF: 0.0116 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.35

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: rs368803931; hg19: chr2-241727459;