4-69595226-C-A

Position:

chr4-69595226-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001105677.2(UGT2A2):c.1047G>T(p.Lys349Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,613,714 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 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 14 hom. )

Consequence

UGT2A2
NM_001105677.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.196

Variant links:

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]

UGT2A2 links:

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]

UGT2A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041841567).

BP6

Variant 4-69595226-C-A is Benign according to our data. Variant chr4-69595226-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 717876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2A2	NM_001105677.2 linkuse as main transcript	c.1047G>T	p.Lys349Asn	missense_variant	4/6	ENST00000604629.6
UGT2A1	NM_001252275.3 linkuse as main transcript	c.1020G>T	p.Lys340Asn	missense_variant	5/7	ENST00000286604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A2	ENST00000604629.6 linkuse as main transcript	c.1047G>T	p.Lys349Asn	missense_variant	4/6	1	NM_001105677.2	P1	P0DTE5-1
UGT2A1	ENST00000286604.9 linkuse as main transcript	c.1020G>T	p.Lys340Asn	missense_variant	5/7	1	NM_001252275.3		P0DTE4-5

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

380

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00428

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00248

AC:

621

AN:

250476

Hom.:

AF XY:

0.00270

AC XY:

366

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00427

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00396

AC:

5788

AN:

1461478

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

2809

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00477

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152236

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00426

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00245

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00241

AC:

293

EpiCase

AF:

0.00409

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.97

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.73

.;T;T;.;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0042

T;T;T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-4.0

D;D;D;D;.;.

REVEL

Benign

0.044

Sift

Benign

0.17

T;T;T;T;.;.

Sift4G

Benign

0.13

T;T;T;T;T;T

Polyphen

0.0010

.;B;.;.;.;.

Vest4

0.17

MutPred

0.41

Loss of methylation at K340 (P = 0.0203);.;.;Loss of methylation at K340 (P = 0.0203);.;.;

MVP

0.11

MPC

0.012

ClinPred

0.012

GERP RS

0.39

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over