22-50523425-T-A

Variant names:

• chr22-50523425-T-A
• rs2782
• NM_152299.4:c.*50T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152299.4(NCAPH2):​c.*50T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCAPH2 NM_152299.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 32 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]

SCO2 (HGNC:10604): (synthesis of cytochrome C oxidase 2) Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. Human COX is a multimeric protein complex that requires several assembly factors; this gene encodes one of the COX assembly factors. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6. [provided by RefSeq, Oct 2014]

SCO2 Gene-Disease associations (from GenCC):

• cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• myopia 6

  Inheritance: AD Classification: STRONG, NO_KNOWN Submitted by: G2P, PanelApp Australia
• autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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 (BayesDel_noAF=-0.84).

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.*50T>A		3_prime_UTR	Exon 20 of 20	NP_689512.2	Q6IBW4-1
	NCAPH2	NM_001185011.2		c.*50T>A		3_prime_UTR	Exon 20 of 20	NP_001171940.1	Q6IBW4-4
	SCO2	NM_005138.3	MANE Select	c.*186A>T		downstream_gene	N/A	NP_005129.2	O43819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPH2	ENST00000420993.7	TSL:1 MANE Select	c.*50T>A		3_prime_UTR	Exon 20 of 20	ENSP00000410088.2	Q6IBW4-1
	NCAPH2	ENST00000299821.15	TSL:1	c.*50T>A		3_prime_UTR	Exon 20 of 20	ENSP00000299821.11	Q6IBW4-4
	NCAPH2	ENST00000910458.1		c.*50T>A		3_prime_UTR	Exon 21 of 21	ENSP00000580517.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1367886 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 671540

African (AFR) AF: 0.00 AC: 0 AN: 31090

American (AMR) AF: 0.00 AC: 0 AN: 34246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23542

East Asian (EAS) AF: 0.00 AC: 0 AN: 35448

South Asian (SAS) AF: 0.00 AC: 0 AN: 76112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064888

Other (OTH) AF: 0.00 AC: 0 AN: 56816

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 37446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.51
DANN	Benign	0.68
PhyloP100		-2.2
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

Other links and lift over

dbSNP: rs2782; hg19: chr22-50961854;