Genetic Variant NM_152299.4:c.325G>A (chr22-50517635-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_152299.4(NCAPH2):c.325G>A(p.Gly109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

NCAPH2
NM_152299.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -1.06

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07136655).

BP6

Variant 22-50517635-G-A is Benign according to our data. Variant chr22-50517635-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2344415.Status of the report is criteria_provided_single_submitter, 1 stars.

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.325G>A	p.Gly109Arg	missense	Exon 4 of 20	NP_689512.2	Q6IBW4-1
NCAPH2	NM_001185011.2		c.325G>A	p.Gly109Arg	missense	Exon 4 of 20	NP_001171940.1	Q6IBW4-4
NCAPH2	NM_014551.5		c.325G>A	p.Gly109Arg	missense	Exon 4 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.325G>A	p.Gly109Arg	missense	Exon 4 of 20	ENSP00000410088.2	Q6IBW4-1
NCAPH2	ENST00000299821.15	TSL:1	c.325G>A	p.Gly109Arg	missense	Exon 4 of 20	ENSP00000299821.11	Q6IBW4-4
NCAPH2	ENST00000395698.7	TSL:1	c.325G>A	p.Gly109Arg	missense	Exon 4 of 9	ENSP00000379050.3	Q6IBW4-5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000955

AC:

AN:

251250

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1461764

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000157

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

1112010

Other (OTH)

AF:

0.0000994

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

AF:

0.0000591

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41436

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.8

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.070

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.64

M_CAP

Benign

0.0035

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.090

PhyloP100

-1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

REVEL

Benign

0.018

Sift

Benign

0.40

Sift4G

Benign

0.62

Polyphen

0.0040

Vest4

0.11

MutPred

0.42

Loss of glycosylation at S108 (P = 0.0615)

MVP

0.043

MPC

0.13

ClinPred

0.020

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.13

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over