dbSNP rs153867: KIF2A:c.2150-1699C>T (chr5-62383785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001098511.3(KIF2A):c.2150-1699C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,206 control chromosomes in the GnomAD database, including 100 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 0.030 ( 100 hom., cov: 32)

Consequence

KIF2A
NM_001098511.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.322

Publications

6 publications found

Variant links:

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]

KIF2A links:

ENSG00000288643 (HGNC:):

ENSG00000288643 links:

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]

DIMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0301 (4587/152206) while in subpopulation NFE AF = 0.0458 (3114/68000). AF 95% confidence interval is 0.0445. There are 100 homozygotes in GnomAd4. There are 2206 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4587 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KIF2A	NM_001098511.3 link	c.2150-1699C>T	intron_variant	Intron 20 of 20	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5 link	c.2036-1699C>T	intron_variant	Intron 19 of 19		NP_004511.2
KIF2A	NM_001243953.2 link	c.1979-1699C>T	intron_variant	Intron 19 of 19		NP_001230882.1
KIF2A	NM_001243952.2 link	c.1955-1699C>T	intron_variant	Intron 20 of 20		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8 link	c.2150-1699C>T		intron_variant	Intron 20 of 20	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2 link	n.64+77249C>T		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4588

AN:

152088

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00874

Gnomad AMI

AF:

0.0529

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0423

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0492

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0211

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

GnomAD4 genome

AF:

0.0301

AC:

4587

AN:

152206

Hom.:

100

Cov.:

AF XY:

0.0296

AC XY:

2206

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00871

AC:

362

AN:

41544

American (AMR)

AF:

0.0164

AC:

251

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0423

AC:

147

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0203

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0492

AC:

521

AN:

10580

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3114

AN:

68000

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

235

470

704

939

1174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0389

Hom.:

208

Bravo

AF:

0.0271

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.42

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over