Variant rs4638 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002266.4(KPNA2):c.801A>G(p.Val267=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KPNA2	NM_002266.4 linkuse as main transcript	c.801A>G	p.Val267=	synonymous_variant	7/11	ENST00000330459.8	NP_002257.1
KPNA2	NM_001320611.2 linkuse as main transcript	c.801A>G	p.Val267=	synonymous_variant	7/11		NP_001307540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA2	ENST00000330459.8 linkuse as main transcript	c.801A>G	p.Val267=	synonymous_variant	7/11	1	NM_002266.4	ENSP00000332455	P4

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

GnomAD3 exomes

AF:

0.656

AC:

165025

AN:

251482

Hom.:

56450

AF XY:

0.664

AC XY:

90234

AN XY:

135918

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 SAS exome

AF:

0.649

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

Gnomad4 AFR exome

AF:

0.422

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.739

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.654

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.746

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.623

AC:

94735

AN:

152060

Hom.:

31131

Cov.:

AF XY:

0.619

AC XY:

45984

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.644

Gnomad4 ASJ

AF:

0.733

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.707

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.647

Alfa

AF:

0.691

Hom.:

16024

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

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over