Genetic Variant SLC22A2:c.843-59T>C (chr6-160247357-A-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.843-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 871,950 control chromosomes in the GnomAD database, including 7,137 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 0.14 ( 1543 hom., cov: 33)

Exomes 𝑓: 0.12 ( 5594 hom. )

Consequence

SLC22A2
NM_003058.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

Publications

53 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.843-59T>C		intron	N/A	NP_003049.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.843-59T>C	intron	N/A	ENSP00000355920.3
SLC22A2	ENST00000366952.1	TSL:5	c.780-59T>C	intron	N/A	ENSP00000355919.1
SLC22A2	ENST00000491092.1	TSL:5	n.740-59T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20592

AN:

152072

Hom.:

1531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.0819

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.121

GnomAD4 exome

AF:

0.117

AC:

84501

AN:

719760

Hom.:

5594

AF XY:

0.115

AC XY:

44468

AN XY:

385404

show subpopulations

African (AFR)

AF:

0.200

AC:

3699

AN:

18472

American (AMR)

AF:

0.0583

AC:

2253

AN:

38670

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

1368

AN:

20380

East Asian (EAS)

AF:

0.0751

AC:

2712

AN:

36108

South Asian (SAS)

AF:

0.0855

AC:

5803

AN:

67856

European-Finnish (FIN)

AF:

0.102

AC:

5243

AN:

51160

Middle Eastern (MID)

AF:

0.112

AC:

473

AN:

4230

European-Non Finnish (NFE)

AF:

0.131

AC:

58726

AN:

447262

Other (OTH)

AF:

0.119

AC:

4224

AN:

35622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3570

7139

10709

14278

17848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1008

2016

3024

4032

5040

<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:

0.136

AC:

20640

AN:

152190

Hom.:

1543

Cov.:

AF XY:

0.131

AC XY:

9770

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.194

AC:

8063

AN:

41522

American (AMR)

AF:

0.0878

AC:

1342

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.0907

AC:

470

AN:

5184

South Asian (SAS)

AF:

0.0822

AC:

396

AN:

4820

European-Finnish (FIN)

AF:

0.0949

AC:

1006

AN:

10606

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8795

AN:

67980

Other (OTH)

AF:

0.120

AC:

253

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

914

1829

2743

3658

4572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.125

Hom.:

5228

Bravo

AF:

0.137

Asia WGS

AF:

0.0850

AC:

294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.93

(source)

DANN

Benign

0.37

PhyloP100

-0.063

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over