22-50523425-T-C

Position:

• chr22-50523425-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152299.4(NCAPH2):​c.*50T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,519,792 control chromosomes in the GnomAD database, including 295,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (30920 hom., cov: 34)
  • Exomes 𝑓: 0.62 (264916 hom.)
• Consequence: NCAPH2 NM_152299.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.23

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-50523425-T-C is Benign according to our data. Variant chr22-50523425-T-C is described in ClinVar as [Benign]. Clinvar id is 1292076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAPH2	NM_152299.4	c.*50T>C		3_prime_UTR_variant	20/20	ENST00000420993.7	NP_689512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAPH2	ENST00000420993.7	c.*50T>C		3_prime_UTR_variant	20/20	1	NM_152299.4	ENSP00000410088.2
NCAPH2	ENST00000299821.15	c.*50T>C		3_prime_UTR_variant	20/20	1		ENSP00000299821.11
NCAPH2	ENST00000395701.7	c.*166T>C		3_prime_UTR_variant	19/19	2		ENSP00000379053.3
NCAPH2	ENST00000522304.1	c.*50T>C		3_prime_UTR_variant	5/5	3		ENSP00000430944.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96713 AN: 152030 Hom.: 30916 Cov.: 34

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.623

GnomAD3 exomes AF: 0.643 AC: 85670 AN: 133162 Hom.: 27727 AF XY: 0.647 AC XY: 45511 AN XY: 70392

Gnomad AFR exome AF: 0.653

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.698

Gnomad SAS exome AF: 0.686

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.621 AC: 849779 AN: 1367644 Hom.: 264916 Cov.: 52 AF XY: 0.623 AC XY: 418117 AN XY: 671400

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.610

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.636 AC: 96754 AN: 152148 Hom.: 30920 Cov.: 34 AF XY: 0.641 AC XY: 47701 AN XY: 74376

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.619

Alfa AF: 0.612 Hom.: 28327

Bravo AF: 0.639

Asia WGS AF: 0.626 AC: 2180 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2782; hg19: chr22-50961854;