Variant 2-132781095-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207363.3(NCKAP5):c.5006A>T(p.Asn1669Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,613,724 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

NCKAP5
NM_207363.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.921

Variant links:

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

NCKAP5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0041718483).

BP6

Variant 2-132781095-T-A is Benign according to our data. Variant chr2-132781095-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 726661.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3 linkuse as main transcript	c.5006A>T	p.Asn1669Ile	missense_variant	15/20	ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6 linkuse as main transcript	c.5006A>T	p.Asn1669Ile	missense_variant	15/20	5	NM_207363.3	P1	O14513-1
	ENST00000651100.1 linkuse as main transcript	n.458-33506T>A		intron_variant, non_coding_transcript_variant
NCKAP5	ENST00000409213.5 linkuse as main transcript	c.1093-7201A>T		intron_variant		5			O14513-2
NCKAP5	ENST00000473859.1 linkuse as main transcript	n.219A>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000282

AC:

AN:

248644

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

134894

show subpopulations

Gnomad AFR exome

AF:

0.00389

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000164

AC:

240

AN:

1461490

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.00463

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152234

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.00164

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00314

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000364

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.049

Sift

Benign

0.035

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.058

B;.

Vest4

0.42

MVP

0.068

MPC

0.048

ClinPred

0.049

GERP RS

-1.9

Varity_R

0.13

gMVP

0.17

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over