rs2018358

Variant names:

• chrX-119588061-G-T
• rs2018358
• ENST00000631185.2:c.331-2067G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000631185.2(UBE2A):​c.331-2067G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.70 (19381 hom., 23239 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: UBE2A ENST00000631185.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 2 publications found

Genes affected

UBE2A (HGNC:12472): (ubiquitin conjugating enzyme E2 A) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin-protein ligases. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair, and may play a role in transcriptional regulation. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

UBE2A Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Nascimento type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2A	ENST00000631185.2	c.331-2067G>T		intron_variant	Intron 5 of 5	5		ENSP00000486153.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 77992 AN: 110804 Hom.: 19377 Cov.: 23

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.726

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.704 AC: 78048 AN: 110861 Hom.: 19381 Cov.: 23 AF XY: 0.702 AC XY: 23239 AN XY: 33099

African (AFR) AF: 0.734 AC: 22396 AN: 30511

American (AMR) AF: 0.783 AC: 8178 AN: 10440

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 1825 AN: 2637

East Asian (EAS) AF: 0.760 AC: 2677 AN: 3522

South Asian (SAS) AF: 0.698 AC: 1873 AN: 2684

European-Finnish (FIN) AF: 0.612 AC: 3579 AN: 5850

Middle Eastern (MID) AF: 0.703 AC: 154 AN: 219

European-Non Finnish (NFE) AF: 0.675 AC: 35686 AN: 52833

Other (OTH) AF: 0.730 AC: 1090 AN: 1493

Alfa AF: 0.696 Hom.: 54998

Bravo AF: 0.723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2018358; hg19: chrX-118722024;