rs3755536

Variant names:

• chr2-240766616-G-A
• rs3755536
• NM_001244008.2:c.1684+299C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-240766616-G-A
• chr2-240766616-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379631.1(KIF1A):​c.1759+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,894 control chromosomes in the GnomAD database, including 6,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6029 hom., cov: 32)
• Consequence: KIF1A NM_001379631.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-240766616-G-A is Benign according to our data. Variant chr2-240766616-G-A is described in ClinVar as Benign. ClinVar VariationId is 683900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379631.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	NM_001244008.2	MANE Select	c.1684+299C>T		intron	N/A	NP_001230937.1
	KIF1A	NM_001379631.1		c.1759+299C>T		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.1657+299C>T		intron	N/A	NP_001366571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.1684+299C>T		intron	N/A	ENSP00000438388.1
	KIF1A	ENST00000675932.2		c.1684+299C>T		intron	N/A	ENSP00000502786.2
	KIF1A	ENST00000675314.2		c.1813+299C>T		intron	N/A	ENSP00000502584.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41975 AN: 151774 Hom.: 6030 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.276 AC: 41981 AN: 151894 Hom.: 6029 Cov.: 32 AF XY: 0.277 AC XY: 20597 AN XY: 74236

African (AFR) AF: 0.258 AC: 10682 AN: 41416

American (AMR) AF: 0.274 AC: 4183 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2854 AN: 5144

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2883 AN: 10544

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18481 AN: 67934

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.281 Hom.: 2686

Bravo AF: 0.273

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		0.057
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: rs3755536; hg19: chr2-241706033;