rs3194481

Variant names:

• chr5-62348135-G-A
• rs3194481
• NM_001098511.3:c.247G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-62348135-G-A
• chr5-62348135-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098511.3(KIF2A):​c.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A83S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF2A NM_001098511.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.101
• Publications: 0 publications found

Genes affected

KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288643 (HGNC:):

DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.012268186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098511.3. 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
	KIF2A	NM_001098511.3	MANE Select	c.247G>A	p.Ala83Thr	missense	Exon 3 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.247G>A	p.Ala83Thr	missense	Exon 3 of 20	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.247G>A	p.Ala83Thr	missense	Exon 3 of 20	NP_001230882.1	A0A6Q8PFA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.247G>A	p.Ala83Thr	missense	Exon 3 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.247G>A	p.Ala83Thr	missense	Exon 3 of 20	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000381103.7	TSL:1	c.166G>A	p.Ala56Thr	missense	Exon 4 of 21	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.97
DANN	Benign	0.39
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.10
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.086
Sift	Benign	0.65	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.16		Gain of glycosylation at A83 (P = 0.0042)
MVP		0.46
MPC		0.83
ClinPred		0.041	T
GERP RS		-6.3
Varity_R		0.019
gMVP		0.14
Mutation Taster		=91/9	polymorphism

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: rs3194481; hg19: chr5-61643962;