chr22-50517802-C-T

Variant names:

• chr22-50517802-C-T
• rs138318301
• NM_152299.4:c.413C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152299.4(NCAPH2):​c.413C>T​(p.Thr138Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,884 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: NCAPH2 NM_152299.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.223
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049880147).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	NM_152299.4	MANE Select	c.413C>T	p.Thr138Met	missense	Exon 5 of 20	NP_689512.2	Q6IBW4-1
	NCAPH2	NM_001185011.2		c.413C>T	p.Thr138Met	missense	Exon 5 of 20	NP_001171940.1	Q6IBW4-4
	NCAPH2	NM_014551.5		c.413C>T	p.Thr138Met	missense	Exon 5 of 9	NP_055366.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	ENST00000420993.7	TSL:1 MANE Select	c.413C>T	p.Thr138Met	missense	Exon 5 of 20	ENSP00000410088.2	Q6IBW4-1
	NCAPH2	ENST00000299821.15	TSL:1	c.413C>T	p.Thr138Met	missense	Exon 5 of 20	ENSP00000299821.11	Q6IBW4-4
	NCAPH2	ENST00000395698.7	TSL:1	c.413C>T	p.Thr138Met	missense	Exon 5 of 9	ENSP00000379050.3	Q6IBW4-5

Frequencies

GnomAD3 genomes AF: 0.0000722 AC: 11 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000723 AC: 18 AN: 249116 AF XY: 0.0000593

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000536

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461514 Hom.: 0 Cov.: 33 AF XY: 0.0000344 AC XY: 25 AN XY: 727018

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86242

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53124

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111968

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152370 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74510

African (AFR) AF: 0.0000721 AC: 3 AN: 41586

American (AMR) AF: 0.000327 AC: 5 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000414 Hom.: 0

Bravo AF: 0.000106

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.8
DANN	Benign	0.93
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.22
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.064
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.71	P
Vest4		0.18
MVP		0.043
MPC		0.18
ClinPred		0.020	T
GERP RS		-1.1
Varity_R		0.012
gMVP		0.13
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138318301; hg19: chr22-50956231;