rs1114167426

Variant names:

• chr19-48552325-T-A
• rs1114167426
• NM_177973.2:c.71+2T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_177973.2(SULT2B1):​c.71+2T>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULT2B1 NM_177973.2 splice_donor, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.49
• Publications: 2 publications found

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

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-48552325-T-A is Pathogenic according to our data. Variant chr19-48552325-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 426110.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.71+2T>A		splice_donor_variant, intron_variant	Intron 1 of 6	ENST00000201586.7	NP_814444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.71+2T>A		splice_donor_variant, intron_variant	Intron 1 of 6	1	NM_177973.2	ENSP00000201586.2
ENSG00000287603	ENST00000666424.1	n.494-1792A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive congenital ichthyosis 2 Pathogenic:1

Jul 01, 2016

Institute for Human Genetics, University Medical Center Freiburg

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A 6- and 10-year-old female and male (siblings) with autosomal recessive congenital ichthyosis manifesting as congenital ichthyosiform erythroderma (ARCI2; 242100) presented the homozygous splice site mutation c.71+2T>A in SULT2B1. -

Ichthyosis, congenital, autosomal recessive 14 Pathogenic:1

Jul 13, 2017

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	33
DANN	Uncertain	0.97
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.78	D
PhyloP100		3.5
GERP RS		3.8
PromoterAI		-0.56	Under-expression
Mutation Taster		=19/81	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.78		Position offset: 43
DS_DL_spliceai		0.99		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1114167426; hg19: chr19-49055582;