dbSNP rs4638: KPNA2:p.Val267Val (chr17-68043234-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002266.4(KPNA2):c.801A>G(p.Val267Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,726 control chromosomes in the GnomAD database, including 409,002 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 0.62 ( 31131 hom., cov: 32)

Exomes 𝑓: 0.71 ( 377871 hom. )

Consequence

KPNA2
NM_002266.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

24 publications found

Variant links:

Genes affected

KPNA2 (HGNC:6395): (karyopherin subunit alpha 2) The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

KPNA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA2	NM_002266.4 link	c.801A>G	p.Val267Val	synonymous_variant	Exon 7 of 11	ENST00000330459.8	NP_002257.1	P52292
KPNA2	NM_001320611.3 link	c.801A>G	p.Val267Val	synonymous_variant	Exon 7 of 11		NP_001307540.1	P52292

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA2	ENST00000330459.8 link	c.801A>G	p.Val267Val	synonymous_variant	Exon 7 of 11	1	NM_002266.4	ENSP00000332455.3		P52292

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

94719

AN:

151942

Hom.:

31131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.707

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.652

GnomAD2 exomes

AF:

0.656

AC:

165025

AN:

251482

AF XY:

0.664

show subpopulations

Gnomad AFR exome

AF:

0.429

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.741

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.706

Gnomad NFE exome

AF:

0.739

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.713

AC:

1041648

AN:

1461666

Hom.:

377871

Cov.:

AF XY:

0.712

AC XY:

517964

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.422

AC:

14133

AN:

33474

American (AMR)

AF:

0.639

AC:

28594

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

19324

AN:

26134

East Asian (EAS)

AF:

0.281

AC:

11144

AN:

39700

South Asian (SAS)

AF:

0.654

AC:

56409

AN:

86256

European-Finnish (FIN)

AF:

0.715

AC:

38213

AN:

53420

Middle Eastern (MID)

AF:

0.649

AC:

3743

AN:

5768

European-Non Finnish (NFE)

AF:

0.746

AC:

829087

AN:

1111802

Other (OTH)

AF:

0.679

AC:

41001

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16954

33909

50863

67818

84772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20036

40072

60108

80144

100180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.623

AC:

94735

AN:

152060

Hom.:

31131

Cov.:

AF XY:

0.619

AC XY:

45984

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.432

AC:

17919

AN:

41446

American (AMR)

AF:

0.644

AC:

9841

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

2544

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1459

AN:

5170

South Asian (SAS)

AF:

0.638

AC:

3079

AN:

4824

European-Finnish (FIN)

AF:

0.707

AC:

7474

AN:

10576

Middle Eastern (MID)

AF:

0.675

AC:

197

AN:

292

European-Non Finnish (NFE)

AF:

0.736

AC:

50067

AN:

67990

Other (OTH)

AF:

0.647

AC:

1362

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1677

3355

5032

6710

8387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.688

Hom.:

16105

Bravo

AF:

0.610

Asia WGS

AF:

0.480

AC:

1669

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.5

(source)

DANN

Benign

0.65

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over