Genetic Variant NCAPH2:p.Gly256Ser (chr22-50519225-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152299.4(NCAPH2):c.766G>A(p.Gly256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NCAPH2
NM_152299.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.649

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115053).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152299.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPH2	NM_152299.4	MANE Select	c.766G>A	p.Gly256Ser	missense	Exon 9 of 20	NP_689512.2	Q6IBW4-1
NCAPH2	NM_001185011.2		c.766G>A	p.Gly256Ser	missense	Exon 9 of 20	NP_001171940.1	Q6IBW4-4
NCAPH2	NM_014551.5		c.766G>A	p.Gly256Ser	missense	Exon 9 of 9	NP_055366.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCAPH2	ENST00000420993.7	TSL:1 MANE Select	c.766G>A	p.Gly256Ser	missense	Exon 9 of 20	ENSP00000410088.2	Q6IBW4-1
NCAPH2	ENST00000299821.15	TSL:1	c.766G>A	p.Gly256Ser	missense	Exon 9 of 20	ENSP00000299821.11	Q6IBW4-4
NCAPH2	ENST00000395698.7	TSL:1	c.766G>A	p.Gly256Ser	missense	Exon 9 of 9	ENSP00000379050.3	Q6IBW4-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458438

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

85576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111078

Other (OTH)

AF:

0.00

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.61

M_CAP

Benign

0.0059

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.65

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.065

Sift

Benign

0.10

Sift4G

Benign

0.065

Polyphen

0.62

Vest4

0.12

MutPred

0.46

Gain of phosphorylation at G256 (P = 0.0039)

MVP

0.082

MPC

0.12

ClinPred

0.31

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.11

Mutation Taster

=94/6

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over