Genetic Variant SLC22A2:c.*489A>C (chr6-160216943-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003058.4(SLC22A2):c.*489A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 151,916 control chromosomes in the GnomAD database, including 40,652 homozygotes. 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 0.72 ( 40652 hom., cov: 32)

Exomes 𝑓: 0.80 ( 24 hom. )

Failed GnomAD Quality Control

Consequence

SLC22A2
NM_003058.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

11 publications found

Variant links:

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

SLC22A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A2	NM_003058.4 link	c.*489A>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC22A2	ENST00000366953.8 link	c.*489A>C	3_prime_UTR_variant	Exon 11 of 11	1	NM_003058.4	ENSP00000355920.3
SLC22A2	ENST00000486916.5 link	n.640+7762A>C	intron_variant	Intron 5 of 5	3
SLC22A2	ENST00000498556.1 link	n.*71A>C	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

108914

AN:

151798

Hom.:

40622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.824

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.755

Gnomad NFE

AF:

0.781

Gnomad OTH

AF:

0.742

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.803

AC:

AN:

Hom.:

Cov.:

AF XY:

0.900

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.767

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.717

AC:

108991

AN:

151916

Hom.:

40652

Cov.:

AF XY:

0.725

AC XY:

53846

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.508

AC:

21007

AN:

41348

American (AMR)

AF:

0.824

AC:

12580

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2915

AN:

3472

East Asian (EAS)

AF:

0.829

AC:

4290

AN:

5174

South Asian (SAS)

AF:

0.782

AC:

3763

AN:

4814

European-Finnish (FIN)

AF:

0.836

AC:

8832

AN:

10564

Middle Eastern (MID)

AF:

0.760

AC:

222

AN:

292

European-Non Finnish (NFE)

AF:

0.781

AC:

53065

AN:

67972

Other (OTH)

AF:

0.746

AC:

1569

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1445

2890

4335

5780

7225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.773

Hom.:

125871

Bravo

AF:

0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.68

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over