7-103352579-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002803.4(PSMC2):c.71-1342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,386 control chromosomes in the GnomAD database, including 5,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (5192 hom., cov: 29)
• Consequence: PSMC2 NM_002803.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.429

Genes affected

PSMC2 (HGNC:9548): (proteasome 26S subunit, ATPase 2) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit has been shown to interact with several of the basal transcription factors so, in addition to participation in proteasome functions, this subunit may participate in the regulation of transcription. This subunit may also compete with PSMC3 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-103352579-A-G is Benign according to our data. Variant chr7-103352579-A-G is described in ClinVar as [Benign]. Clinvar id is 1249575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC2	NM_002803.4	c.71-1342A>G		intron_variant		ENST00000292644.5
PSMC2	NM_001204453.1	c.71-1342A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC2	ENST00000292644.5	c.71-1342A>G		intron_variant		1	NM_002803.4	P3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32579 AN: 151268 Hom.: 5174 Cov.: 29

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32638 AN: 151386 Hom.: 5192 Cov.: 29 AF XY: 0.213 AC XY: 15787 AN XY: 73970

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.184

Alfa AF: 0.0638 Hom.: 78

Bravo AF: 0.230

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.1
Dann	Benign	0.83

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: rs11978339; hg19: chr7-102993026;