NM_001105677.2:c.1198G>A

Variant names:

• chr4-69594610-C-T
• rs4148304
• NM_001105677.2:c.1198G>A

Variant summary

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

The NM_001105677.2(UGT2A2):​c.1198G>A​(p.Val400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,613,992 control chromosomes in the GnomAD database, including 23,886 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1701 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22185 hom.)
• Consequence: UGT2A2 NM_001105677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020368397).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2A2	NM_001105677.2	c.1198G>A	p.Val400Ile	missense_variant	Exon 5 of 6	ENST00000604629.6	NP_001099147.2
UGT2A1	NM_001252275.3	c.1171G>A	p.Val391Ile	missense_variant	Exon 6 of 7	ENST00000286604.9	NP_001239204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2A2	ENST00000604629.6	c.1198G>A	p.Val400Ile	missense_variant	Exon 5 of 6	1	NM_001105677.2	ENSP00000475028.2
UGT2A1	ENST00000286604.9	c.1171G>A	p.Val391Ile	missense_variant	Exon 6 of 7	1	NM_001252275.3	ENSP00000286604.4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21287 AN: 152034 Hom.: 1699 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.142 AC: 35776 AN: 251274 AF XY: 0.143

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.0444

Gnomad EAS exome AF: 0.0246

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.169 AC: 246545 AN: 1461840 Hom.: 22185 Cov.: 33 AF XY: 0.168 AC XY: 122032 AN XY: 727216

African (AFR) AF: 0.103 AC: 3444 AN: 33480

American (AMR) AF: 0.154 AC: 6890 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 1167 AN: 26134

East Asian (EAS) AF: 0.0256 AC: 1015 AN: 39692

South Asian (SAS) AF: 0.150 AC: 12918 AN: 86256

European-Finnish (FIN) AF: 0.139 AC: 7439 AN: 53416

Middle Eastern (MID) AF: 0.0827 AC: 477 AN: 5768

European-Non Finnish (NFE) AF: 0.184 AC: 204381 AN: 1111994

Other (OTH) AF: 0.146 AC: 8814 AN: 60390

GnomAD4 genome AF: 0.140 AC: 21305 AN: 152152 Hom.: 1701 Cov.: 32 AF XY: 0.137 AC XY: 10211 AN XY: 74370

African (AFR) AF: 0.110 AC: 4575 AN: 41510

American (AMR) AF: 0.127 AC: 1945 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3472

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5184

South Asian (SAS) AF: 0.135 AC: 651 AN: 4822

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12075 AN: 67980

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.150 Hom.: 5572

Bravo AF: 0.137

TwinsUK AF: 0.190 AC: 705

ALSPAC AF: 0.184 AC: 710

ESP6500AA AF: 0.103 AC: 453

ESP6500EA AF: 0.175 AC: 1506

ExAC AF: 0.142 AC: 17280

Asia WGS AF: 0.0880 AC: 305 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.35
DANN	Benign	0.79
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.63	.;T;T;.;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.20
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.51	N;N;N;N;.;.
REVEL	Benign	0.052
Sift	Benign	1.0	T;T;T;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0030	.;B;.;.;.;.
Vest4		0.036
MPC		0.011
ClinPred		0.00048	T
GERP RS		-2.7
gMVP		0.086
Mutation Taster		=97/3	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: rs4148304; hg19: chr4-70460328; COSMIC: COSV54138782; COSMIC: COSV54138782;