rs2782

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-50523425-T-C
• chr22-50523425-T-A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 VariationId 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.

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>C		3_prime_UTR	Exon 20 of 20	NP_689512.2	Q6IBW4-1
	NCAPH2	NM_001185011.2		c.*50T>C		3_prime_UTR	Exon 20 of 20	NP_001171940.1	Q6IBW4-4
	SCO2	NM_005138.3	MANE Select	c.*186A>G		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>C		3_prime_UTR	Exon 20 of 20	ENSP00000410088.2	Q6IBW4-1
	NCAPH2	ENST00000299821.15	TSL:1	c.*50T>C		3_prime_UTR	Exon 20 of 20	ENSP00000299821.11	Q6IBW4-4
	NCAPH2	ENST00000910458.1		c.*50T>C		3_prime_UTR	Exon 21 of 21	ENSP00000580517.1

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

GnomAD2 exomes AF: 0.643 AC: 85670 AN: 133162 AF XY: 0.647

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 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

African (AFR) AF: 0.647 AC: 20112 AN: 31088

American (AMR) AF: 0.654 AC: 22372 AN: 34230

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 15444 AN: 23532

East Asian (EAS) AF: 0.717 AC: 25410 AN: 35446

South Asian (SAS) AF: 0.684 AC: 52053 AN: 76082

European-Finnish (FIN) AF: 0.638 AC: 25762 AN: 40352

Middle Eastern (MID) AF: 0.709 AC: 3788 AN: 5346

European-Non Finnish (NFE) AF: 0.610 AC: 649233 AN: 1064766

Other (OTH) AF: 0.627 AC: 35605 AN: 56802

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

African (AFR) AF: 0.652 AC: 27081 AN: 41522

American (AMR) AF: 0.653 AC: 9984 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2326 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3675 AN: 5176

South Asian (SAS) AF: 0.671 AC: 3239 AN: 4828

European-Finnish (FIN) AF: 0.660 AC: 6988 AN: 10594

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41390 AN: 67958

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.616 Hom.: 37446

Bravo AF: 0.639

Asia WGS AF: 0.626 AC: 2180 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.53
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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;