rs150848863

Variant names:

• chr4-69594602-C-T
• rs150848863
• NM_001105677.2:c.1206G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001105677.2(UGT2A2):​c.1206G>A​(p.Met402Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00087 in 1,614,148 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (8 hom.)
• Consequence: UGT2A2 NM_001105677.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0490
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008647591).
• BP6: Variant 4-69594602-C-T is Benign according to our data. Variant chr4-69594602-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 780463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105677.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	NM_001105677.2	MANE Select	c.1206G>A	p.Met402Ile	missense	Exon 5 of 6	NP_001099147.2	P0DTE5-1
	UGT2A1	NM_001252275.3	MANE Select	c.1179G>A	p.Met393Ile	missense	Exon 6 of 7	NP_001239204.2	P0DTE4-5
	UGT2A1	NM_001389565.1		c.1809G>A	p.Met603Ile	missense	Exon 7 of 8	NP_001376494.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	ENST00000604629.6	TSL:1 MANE Select	c.1206G>A	p.Met402Ile	missense	Exon 5 of 6	ENSP00000475028.2	P0DTE5-1
	UGT2A1	ENST00000286604.9	TSL:1 MANE Select	c.1179G>A	p.Met393Ile	missense	Exon 6 of 7	ENSP00000286604.4	P0DTE4-5
	UGT2A1	ENST00000503640.5	TSL:1	c.1179G>A	p.Met393Ile	missense	Exon 5 of 6	ENSP00000424478.1	P0DTE4-1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00140 AC: 351 AN: 251312 AF XY: 0.00110

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000503 AC: 735 AN: 1461854 Hom.: 8 Cov.: 31 AF XY: 0.000452 AC XY: 329 AN XY: 727222

African (AFR) AF: 0.0135 AC: 453 AN: 33480

American (AMR) AF: 0.00172 AC: 77 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1112004

Other (OTH) AF: 0.00189 AC: 114 AN: 60392

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152294 Hom.: 6 Cov.: 32 AF XY: 0.00431 AC XY: 321 AN XY: 74462

African (AFR) AF: 0.0148 AC: 614 AN: 41560

American (AMR) AF: 0.00268 AC: 41 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00221 Hom.: 0

Bravo AF: 0.00520

ESP6500AA AF: 0.0143 AC: 63

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00179 AC: 217

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.068
Eigen_PC	Benign	0.092
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.049
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.067
Sift	Benign	0.065	T
Sift4G	Uncertain	0.032	D
Polyphen		0.0090	B
Vest4		0.17
MutPred		0.66		Gain of sheet (P = 0.0827)
MVP		0.40
MPC		0.011
ClinPred		0.019	T
GERP RS		4.5
gMVP		0.23
Mutation Taster		=93/7	polymorphism

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: rs150848863; hg19: chr4-70460320;