rs6732174

Variant names:

• chr2-240792123-C-T
• rs6732174
• NM_001244008.2:c.107-2811G>A

Variant summary

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

The NM_001244008.2(KIF1A):​c.107-2811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,934 control chromosomes in the GnomAD database, including 4,806 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 0.25 (4806 hom., cov: 31)
• Consequence: KIF1A NM_001244008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• hereditary spastic paraplegia 30

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1A	NM_001244008.2	MANE Select	c.107-2811G>A		intron	N/A	NP_001230937.1	Q12756-3
	KIF1A	NM_001379631.1		c.107-2811G>A		intron	N/A	NP_001366560.1
	KIF1A	NM_001379642.1		c.107-2811G>A		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.107-2811G>A		intron	N/A	ENSP00000438388.1	Q12756-3
	KIF1A	ENST00000675932.2		c.107-2811G>A		intron	N/A	ENSP00000502786.2	A0A6Q8PHQ5
	KIF1A	ENST00000675314.2		c.107-2811G>A		intron	N/A	ENSP00000502584.2	A0A6Q8PH56

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37590 AN: 151816 Hom.: 4804 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.247 AC: 37586 AN: 151934 Hom.: 4806 Cov.: 31 AF XY: 0.246 AC XY: 18263 AN XY: 74256

African (AFR) AF: 0.197 AC: 8169 AN: 41442

American (AMR) AF: 0.198 AC: 3030 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.152 AC: 782 AN: 5150

South Asian (SAS) AF: 0.198 AC: 952 AN: 4808

European-Finnish (FIN) AF: 0.335 AC: 3545 AN: 10578

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19521 AN: 67898

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.268 Hom.: 906

Bravo AF: 0.235

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-2.5
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

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

Other links and lift over

dbSNP: rs6732174;

hg19: chr2-241731540;