2-240757423-ATCCTCCTCCTCCTCCTCC-ATCCTCCTCCTCCTCCTCCTCCTCCTCC

Variant names:

• chr2-240757423-A-ATCCTCCTCC
• rs10594016
• NM_001244008.2:c.2745_2753dupGGAGGAGGA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001244008.2(KIF1A):​c.2745_2753dupGGAGGAGGA​(p.Glu915_Glu917dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: KIF1A NM_001244008.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 17 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, G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

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

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

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001244008.2

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	NM_001244008.2	MANE Select	c.2745_2753dupGGAGGAGGA	p.Glu915_Glu917dup	disruptive_inframe_insertion	Exon 27 of 49	NP_001230937.1	Q12756-3
	KIF1A	NM_001379631.1		c.2820_2828dupGGAGGAGGA	p.Glu940_Glu942dup	disruptive_inframe_insertion	Exon 27 of 49	NP_001366560.1
	KIF1A	NM_001379642.1		c.2718_2726dupGGAGGAGGA	p.Glu906_Glu908dup	disruptive_inframe_insertion	Exon 26 of 49	NP_001366571.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	ENST00000498729.9	TSL:5 MANE Select	c.2745_2753dupGGAGGAGGA	p.Glu915_Glu917dup	disruptive_inframe_insertion	Exon 27 of 49	ENSP00000438388.1	Q12756-3
	KIF1A	ENST00000675932.2		c.2745_2753dupGGAGGAGGA	p.Glu915_Glu917dup	disruptive_inframe_insertion	Exon 27 of 49	ENSP00000502786.2	A0A6Q8PHQ5
	KIF1A	ENST00000675314.2		c.2874_2882dupGGAGGAGGA	p.Glu958_Glu960dup	disruptive_inframe_insertion	Exon 28 of 50	ENSP00000502584.2	A0A6Q8PH56

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 2 AN: 137556 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000747

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000161

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000446 AC: 6 AN: 1345204 Hom.: 0 Cov.: 0 AF XY: 0.00000603 AC XY: 4 AN XY: 663330

African (AFR) AF: 0.00 AC: 0 AN: 29382

American (AMR) AF: 0.00 AC: 0 AN: 33864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23936

East Asian (EAS) AF: 0.0000293 AC: 1 AN: 34166

South Asian (SAS) AF: 0.0000266 AC: 2 AN: 75084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5376

European-Non Finnish (NFE) AF: 0.00000288 AC: 3 AN: 1041208

Other (OTH) AF: 0.00 AC: 0 AN: 55836

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 137556 Hom.: 0 Cov.: 0 AF XY: 0.0000300 AC XY: 2 AN XY: 66558

African (AFR) AF: 0.00 AC: 0 AN: 38136

American (AMR) AF: 0.0000747 AC: 1 AN: 13388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3258

East Asian (EAS) AF: 0.00 AC: 0 AN: 4660

South Asian (SAS) AF: 0.00 AC: 0 AN: 4096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000161 AC: 1 AN: 62056

Other (OTH) AF: 0.00 AC: 0 AN: 1888

Alfa AF: 0.00 Hom.: 1564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=86/14	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10594016; hg19: chr2-241696840;