chr22-50518194-C-G

Position:

• chr22-50518194-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152299.4(NCAPH2):​c.562C>G​(p.Pro188Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCAPH2 NM_152299.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPH2	NM_152299.4	c.562C>G	p.Pro188Ala	missense_variant	7/20	ENST00000420993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPH2	ENST00000420993.7	c.562C>G	p.Pro188Ala	missense_variant	7/20	1	NM_152299.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.562C>G (p.P188A) alteration is located in exon 7 (coding exon 7) of the NCAPH2 gene. This alteration results from a C to G substitution at nucleotide position 562, causing the proline (P) at amino acid position 188 to be replaced by an alanine (A). 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	0.079
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T;.;T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.82	N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.035	D;T;D;T;D
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		1.0	D;P;.;.;D
Vest4		0.34
MutPred		0.85		Gain of MoRF binding (P = 0.0454);Gain of MoRF binding (P = 0.0454);Gain of MoRF binding (P = 0.0454);.;Gain of MoRF binding (P = 0.0454);
MVP		0.22
MPC		0.12
ClinPred		0.51	D
GERP RS		4.2
Varity_R		0.050
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50956623;