Variant chr22-50518180-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152299.4(NCAPH2):c.548C>T(p.Thr183Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NCAPH2
NM_152299.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

NCAPH2 (HGNC:25071): (non-SMC condensin II complex subunit H2) This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.[provided by RefSeq, May 2010]

NCAPH2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPH2	NM_152299.4 linkuse as main transcript	c.548C>T	p.Thr183Met	missense_variant	7/20	ENST00000420993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPH2	ENST00000420993.7 linkuse as main transcript	c.548C>T	p.Thr183Met	missense_variant	7/20	1	NM_152299.4	P4	Q6IBW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250766

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.548C>T (p.T183M) alteration is located in exon 7 (coding exon 7) of the NCAPH2 gene. This alteration results from a C to T substitution at nucleotide position 548, causing the threonine (T) at amino acid position 183 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.67

D;.;T;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.83

D;D;D;D;D

MetaSVM

Uncertain

-0.067

MutationAssessor

Uncertain

2.8

M;M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.6

D;D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.019

D;D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D

Polyphen

1.0

D;D;.;.;D

Vest4

0.66

MutPred

0.74

Loss of glycosylation at T183 (P = 0.0062);Loss of glycosylation at T183 (P = 0.0062);Loss of glycosylation at T183 (P = 0.0062);.;Loss of glycosylation at T183 (P = 0.0062);

MVP

0.31

MPC

0.53

ClinPred

0.94

GERP RS

5.2

Varity_R

0.16

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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