chr19-48596914-G-A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_177973.2(SULT2B1):c.821G>A(p.Arg274Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,587,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SULT2B1
NM_177973.2 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.68

Publications

6 publications found

Variant links:

Genes affected

SULT2B1 (HGNC:11459): (sulfotransferase family 2B member 1) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

SULT2B1 Gene-Disease associations (from GenCC):

ichthyosis, congenital, autosomal recessive 14
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SULT2B1 links:

ENSG00000287603 (HGNC:):

ENSG00000287603 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

PP5

Variant 19-48596914-G-A is Pathogenic according to our data. Variant chr19-48596914-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 426108.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177973.2. 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
	SULT2B1	NM_177973.2	MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 6 of 7	NP_814444.1
	SULT2B1	NM_004605.2		c.776G>A	p.Arg259Gln	missense	Exon 5 of 6	NP_004596.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.821G>A	p.Arg274Gln	missense	Exon 6 of 7	ENSP00000201586.2
SULT2B1	ENST00000323090.4	TSL:1	c.776G>A	p.Arg259Gln	missense	Exon 5 of 6	ENSP00000312880.3
SULT2B1	ENST00000594274.1	TSL:3	n.571G>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000472

AC:

AN:

211864

AF XY:

0.00000869

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1435618

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

713410

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33268

American (AMR)

AF:

0.00

AC:

AN:

41808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25700

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39080

South Asian (SAS)

AF:

0.00

AC:

AN:

83906

European-Finnish (FIN)

AF:

0.000118

AC:

AN:

42482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5200

European-Non Finnish (NFE)

AF:

0.00000905

AC:

AN:

1104528

Other (OTH)

AF:

0.0000168

AC:

AN:

59646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive congenital ichthyosis 2 (1)

Ichthyosis, congenital, autosomal recessive 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.99

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.9

PhyloP100

7.7

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.98

Loss of MoRF binding (P = 0.0351)

MVP

0.49

MPC

1.0

ClinPred

1.0

GERP RS

4.3

Varity_R

0.94

gMVP

0.79

Mutation Taster

=61/39

disease causing (ClinVar)

(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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over