2-240783028-G-A

Variant names:

• chr2-240783028-G-A
• rs2288750
• NM_001244008.2:c.864+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244008.2(KIF1A):​c.864+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,604,656 control chromosomes in the GnomAD database, including 39,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6631 hom., cov: 34)
  • Exomes 𝑓: 0.21 (33223 hom.)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.763
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP6: Variant 2-240783028-G-A is Benign according to our data. Variant chr2-240783028-G-A is described in ClinVar as Benign. ClinVar VariationId is 283505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 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.864+16C>T		intron	N/A	NP_001230937.1
	KIF1A	NM_001379631.1		c.864+16C>T		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.864+16C>T		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.864+16C>T		intron	N/A	ENSP00000438388.1
	KIF1A	ENST00000675932.2		c.864+16C>T		intron	N/A	ENSP00000502786.2
	KIF1A	ENST00000675314.2		c.993+16C>T		intron	N/A	ENSP00000502584.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41401 AN: 152006 Hom.: 6623 Cov.: 34

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.219 AC: 54419 AN: 248348 AF XY: 0.207

Gnomad AFR exome AF: 0.443

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.327

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.205 AC: 297905 AN: 1452532 Hom.: 33223 Cov.: 31 AF XY: 0.200 AC XY: 144972 AN XY: 723286

African (AFR) AF: 0.454 AC: 15088 AN: 33268

American (AMR) AF: 0.267 AC: 11934 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5147 AN: 26082

East Asian (EAS) AF: 0.374 AC: 14809 AN: 39634

South Asian (SAS) AF: 0.107 AC: 9236 AN: 86102

European-Finnish (FIN) AF: 0.171 AC: 9035 AN: 52972

Middle Eastern (MID) AF: 0.206 AC: 1187 AN: 5754

European-Non Finnish (NFE) AF: 0.198 AC: 218513 AN: 1103902

Other (OTH) AF: 0.216 AC: 12956 AN: 60114

GnomAD4 genome AF: 0.272 AC: 41421 AN: 152124 Hom.: 6631 Cov.: 34 AF XY: 0.268 AC XY: 19904 AN XY: 74368

African (AFR) AF: 0.444 AC: 18442 AN: 41490

American (AMR) AF: 0.271 AC: 4146 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1744 AN: 5152

South Asian (SAS) AF: 0.107 AC: 514 AN: 4812

European-Finnish (FIN) AF: 0.159 AC: 1688 AN: 10616

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13451 AN: 67976

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.209 Hom.: 7424

Bravo AF: 0.290

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Sep 22, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.67
PhyloP100		-0.76
PromoterAI		0.033	Neutral
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: rs2288750; hg19: chr2-241722445;