4-69594611-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001105677.2(UGT2A2):c.1197A>T(p.Gly399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,614,116 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (7 hom.)
• Consequence: UGT2A2 NM_001105677.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.71

Genes affected

UGT2A2 (HGNC:28183): (UDP glucuronosyltransferase family 2 member A2) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A1 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

UGT2A1 (HGNC:12542): (UDP glucuronosyltransferase family 2 member A1 complex locus) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 4-69594611-T-A is Benign according to our data. Variant chr4-69594611-T-A is described in ClinVar as [Benign]. Clinvar id is 788781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.71 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2A2	NM_001105677.2	c.1197A>T	p.Gly399=	synonymous_variant	5/6	ENST00000604629.6
UGT2A1	NM_001252275.3	c.1170A>T	p.Gly390=	synonymous_variant	6/7	ENST00000286604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A2	ENST00000604629.6	c.1197A>T	p.Gly399=	synonymous_variant	5/6	1	NM_001105677.2	P1
UGT2A1	ENST00000286604.9	c.1170A>T	p.Gly390=	synonymous_variant	6/7	1	NM_001252275.3

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 317 AN: 152150 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00395

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00174 AC: 437 AN: 251306 Hom.: 2 AF XY: 0.00174 AC XY: 237 AN XY: 135818

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00312

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00280 AC: 4094 AN: 1461848 Hom.: 7 Cov.: 32 AF XY: 0.00268 AC XY: 1952 AN XY: 727218

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.00209 AC: 319 AN: 152268 Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74452

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00397

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00174

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00284

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

Invitae

Jul 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.6
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs146749264; hg19: chr4-70460329;