chr2-202237622-G-A

Variant names:

• chr2-202237622-G-A
• rs6761234
• NM_003352.8:c.12+818C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003352.8(SUMO1):​c.12+818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,162 control chromosomes in the GnomAD database, including 17,658 homozygotes. 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: 𝑓 0.47 (17658 hom., cov: 34)
• Consequence: SUMO1 NM_003352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 3 publications found

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]

SUMO1 Gene-Disease associations (from GenCC):

• orofacial cleft 10

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMO1	NM_003352.8	c.12+818C>T		intron_variant	Intron 1 of 4	ENST00000392246.7	NP_003343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMO1	ENST00000392246.7	c.12+818C>T		intron_variant	Intron 1 of 4	1	NM_003352.8	ENSP00000376077.2
SUMO1	ENST00000409498.6	c.-199+818C>T		intron_variant	Intron 1 of 5	3		ENSP00000386472.2

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70889 AN: 152044 Hom.: 17641 Cov.: 34

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.466 AC: 70935 AN: 152162 Hom.: 17658 Cov.: 34 AF XY: 0.468 AC XY: 34810 AN XY: 74376

African (AFR) AF: 0.276 AC: 11465 AN: 41512

American (AMR) AF: 0.548 AC: 8378 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3049 AN: 5184

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4826

European-Finnish (FIN) AF: 0.567 AC: 5991 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36561 AN: 67994

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.516 Hom.: 80553

Bravo AF: 0.459

Asia WGS AF: 0.398 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.15
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: rs6761234; hg19: chr2-203102345; COSMIC: COSV107496695;