2-202214584-T-C

Position:

• chr2-202214584-T-C

Variant summary

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

The NM_003352.8(SUMO1):​c.88-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 577,096 control chromosomes in the GnomAD database, including 222,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (58895 hom., cov: 33)
  • Exomes 𝑓: 0.88 (164063 hom.)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.119

Genes affected

SUMO1 (HGNC:12502): (small ubiquitin like modifier 1) This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-202214584-T-C is Benign according to our data. Variant chr2-202214584-T-C is described in ClinVar as [Benign]. Clinvar id is 1258470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMO1	NM_003352.8	c.88-150A>G		intron_variant		ENST00000392246.7	NP_003343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMO1	ENST00000392246.7	c.88-150A>G		intron_variant		1	NM_003352.8	ENSP00000376077	P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133682 AN: 152116 Hom.: 58840 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.861

GnomAD4 exome AF: 0.878 AC: 372898 AN: 424862 Hom.: 164063 AF XY: 0.873 AC XY: 198356 AN XY: 227324

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.916

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.886

Gnomad4 OTH exome AF: 0.873

GnomAD4 genome AF: 0.879 AC: 133796 AN: 152234 Hom.: 58895 Cov.: 33 AF XY: 0.877 AC XY: 65294 AN XY: 74424

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.862

Alfa AF: 0.880 Hom.: 12674

Bravo AF: 0.878

Asia WGS AF: 0.784 AC: 2722 AN: 3468

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.75
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: rs3769817; hg19: chr2-203079307;