2-202238189-A-G

Variant summary

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

The NM_003352.8(SUMO1):c.12+251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,322 control chromosomes in the GnomAD database, including 73,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.98 (73444 hom., cov: 33)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.773

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-202238189-A-G is Benign according to our data. Variant chr2-202238189-A-G is described in ClinVar as [Benign]. Clinvar id is 1258266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMO1	NM_003352.8	c.12+251T>C		intron_variant		ENST00000392246.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMO1	ENST00000392246.7	c.12+251T>C		intron_variant		1	NM_003352.8	P1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149410 AN: 152204 Hom.: 73386 Cov.: 33

Gnomad AFR AF: 0.937

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.987

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

GnomAD4 genome AF: 0.982 AC: 149527 AN: 152322 Hom.: 73444 Cov.: 33 AF XY: 0.982 AC XY: 73168 AN XY: 74484

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.987

Alfa AF: 0.990 Hom.: 15696

Bravo AF: 0.979

Asia WGS AF: 0.998 AC: 3468 AN: 3476

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.1
Dann	Benign	0.33
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: rs10167674; hg19: chr2-203102912;