NM_001098511.3:c.195C>A

Variant names:

• chr5-62348083-C-A
• rs73102041
• NM_001098511.3:c.195C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001098511.3(KIF2A):​c.195C>A​(p.Asp65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,756 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. D65D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0063 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (9 hom.)
• Consequence: KIF2A NM_001098511.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.83
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007913381).
• BP6: Variant 5-62348083-C-A is Benign according to our data. Variant chr5-62348083-C-A is described in ClinVar as Benign. ClinVar VariationId is 382901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00627 (955/152276) while in subpopulation AFR AF = 0.0221 (918/41548). AF 95% confidence interval is 0.0209. There are 8 homozygotes in GnomAd4. There are 464 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 955 AD gene.

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.195C>A	p.Asp65Glu	missense	Exon 3 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.195C>A	p.Asp65Glu	missense	Exon 3 of 20	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.195C>A	p.Asp65Glu	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.195C>A	p.Asp65Glu	missense	Exon 3 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.195C>A	p.Asp65Glu	missense	Exon 3 of 20	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000381103.7	TSL:1	c.114C>A	p.Asp38Glu	missense	Exon 4 of 21	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 954 AN: 152158 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

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: 0.0000588

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00158 AC: 397 AN: 251154 AF XY: 0.00119

Gnomad AFR exome AF: 0.0226

Gnomad AMR exome AF: 0.000752

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000629 AC: 919 AN: 1461480 Hom.: 9 Cov.: 30 AF XY: 0.000552 AC XY: 401 AN XY: 727036

African (AFR) AF: 0.0238 AC: 795 AN: 33468

American (AMR) AF: 0.000872 AC: 39 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111702

Other (OTH) AF: 0.00118 AC: 71 AN: 60358

GnomAD4 genome AF: 0.00627 AC: 955 AN: 152276 Hom.: 8 Cov.: 32 AF XY: 0.00623 AC XY: 464 AN XY: 74458

African (AFR) AF: 0.0221 AC: 918 AN: 41548

American (AMR) AF: 0.00164 AC: 25 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00237 Hom.: 9

Bravo AF: 0.00703

ESP6500AA AF: 0.0207 AC: 91

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00194 AC: 235

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	KIF2A-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.73	N
PhyloP100		1.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.19
Sift	Benign	0.81	T
Sift4G	Benign	0.66	T
Polyphen		0.44	B
Vest4		0.57
MutPred		0.12		Gain of phosphorylation at S61 (P = 0.191)
MVP		0.47
MPC		1.4
ClinPred		0.019	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.32
Mutation Taster		=96/4	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: rs73102041; hg19: chr5-61643910;