2-240752039-G-C

Variant names:

• chr2-240752039-G-C
• rs11693670
• NM_001244008.2:c.2859-1492C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244008.2(KIF1A):​c.2859-1492C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,726 control chromosomes in the GnomAD database, including 16,251 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 0.46 (16251 hom., cov: 31)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 9

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neuropathy, hereditary sensory, type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• hereditary spastic paraplegia 30

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• PEHO syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244008.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	NM_001244008.2	MANE Select	c.2859-1492C>G		intron	N/A	NP_001230937.1
	KIF1A	NM_001379631.1		c.2934-1492C>G		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.2832-1492C>G		intron	N/A	NP_001366571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.2859-1492C>G		intron	N/A	ENSP00000438388.1
	KIF1A	ENST00000675932.2		c.2859-1492C>G		intron	N/A	ENSP00000502786.2
	KIF1A	ENST00000675314.2		c.2988-1492C>G		intron	N/A	ENSP00000502584.2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69616 AN: 151608 Hom.: 16245 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.459 AC: 69636 AN: 151726 Hom.: 16251 Cov.: 31 AF XY: 0.458 AC XY: 33968 AN XY: 74134

African (AFR) AF: 0.407 AC: 16836 AN: 41348

American (AMR) AF: 0.428 AC: 6541 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3466

East Asian (EAS) AF: 0.637 AC: 3246 AN: 5096

South Asian (SAS) AF: 0.363 AC: 1738 AN: 4792

European-Finnish (FIN) AF: 0.472 AC: 4972 AN: 10542

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33028 AN: 67888

Other (OTH) AF: 0.463 AC: 976 AN: 2106

Alfa AF: 0.320 Hom.: 820

Bravo AF: 0.452

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11693670; hg19: chr2-241691456;