2-233768226-C-T

Position:

• chr2-233768226-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3 BP4_Strong BS2

The NM_007120.3(UGT1A4):​c.1094C>T​(p.Pro365Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,614,202 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,other (no stars).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (7 hom.)
• Consequence: UGT1A4 NM_007120.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity; other criteria provided, conflicting classifications P:8 U:4 O:1
• Conservation: PhyloP100: 7.62

Genes affected

UGT1A4 (HGNC:12536): (UDP glucuronosyltransferase family 1 member A4) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins. [provided by RefSeq, Jul 2008]

UGT1A5 (HGNC:12537): (UDP glucuronosyltransferase family 1 member A5) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. [provided by RefSeq, Jul 2008]

UGT1A3 (HGNC:12535): (UDP glucuronosyltransferase family 1 member A3) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq, Jul 2008]

UGT1A1 (HGNC:12530): (UDP glucuronosyltransferase family 1 member A1) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]

UGT1A6 (HGNC:12538): (UDP glucuronosyltransferase family 1 member A6) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]

UGT1A10 (HGNC:12531): (UDP glucuronosyltransferase family 1 member A10) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity on mycophenolic acid, coumarins, and quinolines. [provided by RefSeq, Jul 2008]

UGT1A8 (HGNC:12540): (UDP glucuronosyltransferase family 1 member A8) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity with many substrates including coumarins, phenols, anthraquinones, flavones, and some opioids. [provided by RefSeq, Jul 2008]

UGT1A7 (HGNC:12539): (UDP glucuronosyltransferase family 1 member A7) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has moderate glucuronidase activity with phenols. [provided by RefSeq, Jul 2008]

UGT1A9 (HGNC:12541): (UDP glucuronosyltransferase family 1 member A9) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: BayesDel_noAF, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.019219369).
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A4	NM_007120.3	c.1094C>T	p.Pro365Leu	missense_variant	4/5	ENST00000373409.8	NP_009051.1
UGT1A5	NM_019078.2	c.1094C>T	p.Pro365Leu	missense_variant	4/5	ENST00000373414.4	NP_061951.1
UGT1A3	NM_019093.4	c.1094C>T	p.Pro365Leu	missense_variant	4/5	ENST00000482026.6	NP_061966.1
UGT1A1	NM_000463.3	c.1091C>T	p.Pro364Leu	missense_variant	4/5	ENST00000305208.10	NP_000454.1
UGT1A6	NM_001072.4	c.1088C>T	p.Pro363Leu	missense_variant	4/5	ENST00000305139.11	NP_001063.2
UGT1A10	NM_019075.4	c.1082C>T	p.Pro361Leu	missense_variant	4/5	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.1082C>T	p.Pro361Leu	missense_variant	4/5	ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.1082C>T	p.Pro361Leu	missense_variant	4/5	ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.1082C>T	p.Pro361Leu	missense_variant	4/5	ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A4	ENST00000373409.8	c.1094C>T	p.Pro365Leu	missense_variant	4/5	1	NM_007120.3	ENSP00000362508	P1
UGT1A5	ENST00000373414.4	c.1094C>T	p.Pro365Leu	missense_variant	4/5	1	NM_019078.2	ENSP00000362513	P1
UGT1A3	ENST00000482026.6	c.1094C>T	p.Pro365Leu	missense_variant	4/5	1	NM_019093.4	ENSP00000418532	P1
UGT1A1	ENST00000305208.10	c.1091C>T	p.Pro364Leu	missense_variant	4/5	1	NM_000463.3	ENSP00000304845	P1
UGT1A6	ENST00000305139.11	c.1088C>T	p.Pro363Leu	missense_variant	4/5	1	NM_001072.4	ENSP00000303174	P1
UGT1A10	ENST00000344644.10	c.1082C>T	p.Pro361Leu	missense_variant	4/5	1	NM_019075.4	ENSP00000343838	P1
UGT1A9	ENST00000354728.5	c.1082C>T	p.Pro361Leu	missense_variant	4/5	1	NM_021027.3	ENSP00000346768	P1
UGT1A7	ENST00000373426.4	c.1082C>T	p.Pro361Leu	missense_variant	4/5	1	NM_019077.3	ENSP00000362525	P1
UGT1A8	ENST00000373450.5	c.1082C>T	p.Pro361Leu	missense_variant	4/5	1	NM_019076.5	ENSP00000362549	P1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00124 AC: 309 AN: 249048 Hom.: 2 AF XY: 0.00108 AC XY: 146 AN XY: 134816

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0116

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000629

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000420 AC: 614 AN: 1461890 Hom.: 7 Cov.: 36 AF XY: 0.000421 AC XY: 306 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00907

Gnomad4 SAS exome AF: 0.000916

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74476

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000737 Hom.: 1

Bravo AF: 0.00126

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity; other

Submissions summary: Pathogenic:8 Uncertain:4 Other:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Pathogenic:2 Uncertain:2 Other:1

Pathogenic, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 10, 2022	PP3, PS3, PS4 -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	May 01, 2023	Published functional studies demonstrate a damaging effect with 35.6% enzyme activity compared to wild type (Takeuchi et al., 2004; Mimura et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23875061, 27264814, 30669781, 33083013, 31737051, 20981092, 15304120, 26727668, 29137095, 34426522, 31589614, 35257483, 25993113, 21726413, 35436954, 34953813, 31122244) -
other, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 23, 2018	- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 364 of the UGT1A1 protein (p.Pro364Leu). This variant is present in population databases (rs34946978, gnomAD 1.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Crigler-Najjar syndrome type II and/or Gilbert syndrome (PMID: 15304120, 27264814, 31737051, 34953813, 35257483, 35436954). This variant is also known as UGT1A1*63. ClinVar contains an entry for this variant (Variation ID: 212543). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UGT1A1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects UGT1A1 function (PMID: 15304120). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Pathogenic, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	The UGT1A1 c.1091C>T; p.Pro364Leu variant (rs34946978), also known as UGT1A1*73, has been reported in neonates with severe hyperbilirubinemia (Huang 2002, Yang 2016, Yang 2021), and also in multiple individuals either affected with Gilbert syndrome (Farheen 2006, Sun 2017, Takeuchi 2004) or Crigler-Najjar syndrome (Li 2015, Sun 2017, Yang 2016). In vitro functional analyses of this variant demonstrated a significant reduction in the UGT1A1 enzyme activity (Takeuchi 2004). This variant is also reported in ClinVar (Variation ID: 212543). This variant is found in the general population with an overall allele frequency of 0.1% (334/280448 alleles, including two homozygotes) in the Genome Aggregation Database. The proline at codon 364 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.836). Based on available information, this variant is considered to be pathogenic. References: Farheen S et al. Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol. 2006 Apr 14. PMID: 16610035 Huang CS et al. Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia. Pediatr Res. 2002 Oct. PMID: 12357057 Li L et al. Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II. PLoS One. 2015 PMID: 25993113 Sun L et al. Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II. Medicine (Baltimore). 2017 Nov. PMID: 29137095 Takeuchi K et al. Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects. J Gastroenterol Hepatol. 2004 Sep. PMID: 15304120 Yang H et al. Clinical Significance of UGT1A1 Genetic Analysis in Chinese Neonates with Severe Hyperbilirubinemia. Pediatr Neonatol. 2016 Aug. PMID: 26727668 Yang H et al. UGT1A1 mutation association with increased bilirubin levels and severity of unconjugated hyperbilirubinemia in ABO incompatible newborns of China. BMC pediatrics. 2021 PMID: 34074250 -

Gilbert syndrome Pathogenic:2 Uncertain:1

Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Pathogenic, no assertion criteria provided	case-control	Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing You An Hospital, Capital Medical University	May 01, 2019	- -

Crigler-Najjar syndrome type 1;C0017551:Gilbert syndrome;C0270210:Lucey-Driscoll syndrome;C1866173:Bilirubin, serum level of, quantitative trait locus 1;C2931132:Crigler-Najjar syndrome, type II Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

UGT1A1-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2024

The UGT1A1 c.1091C>T variant is predicted to result in the amino acid substitution p.Pro364Leu. This variant has been reported in the homozygous or compound heterozygous states in patients with Crigler–Najjar syndrome type II (Li et al. 2015. PubMed ID: 25993113; Wu et al. 2016. PubMed ID: 27264814). In other patients with Gilbert’s syndrome (a mild liver disorder), this variant was also reported in the compound heterozygous state along with other well-characterized risk factors for decreased UGT1A1 activity (Takeuchi et al. 2004. PubMed ID: 15304120; Maruo et al. 2014. PubMed ID: 24650397). Functional studies using COS7 cells showed that the p.Pro364Leu substitution reduced UGT1A1 activity by ~ 64% (Takeuchi et al. 2004. PubMed ID: 15304120; Mimura et al. 2011. PubMed ID: 21726413). In ClinVar, this variant was reported to have conflicting interpretations of pathogenicity ranging from uncertain to pathogenic by different laboratories (Variation ID: 212543). In summary, the c.1091C>T variant is categorized as likely pathogenic. -

Hyperbilirubinemia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 22, 2014

- -

Crigler-Najjar syndrome type 1 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Centogene AG - the Rare Disease Company

-

- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jan 16, 2024

Variant summary: UGT1A1 c.1091C>T (p.Pro364Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00045 in 1614202 control chromosomes in the gnomAD database, including 7 homozygotes (gnomAD). c.1091C>T has been reported in the literature in individuals affected with Gilberts Syndrome (example: Takeuchi_2004, Sun_2017, Wang_2022), neonatal unconjugated hyperbilirubinemia (example: Mei_2022, and Cozzi_2022), Crigler-Najjar syndrome type II (example: Sun_2017, and Wu_2016). One study has reported that this variant is a genetic risk factor for unconjugated hyperbilirubinemia (6.8 OR) (Bai_2019). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 35.6% of normal activity (example: Takeuchi_2004, and Mimura_2011). The following publications have been ascertained in the context of this evaluation (PMID: 12105841, 34953813, 21726413, 29137095, 15304120, 31450232, 27264814, 26727668, 35436954, 33083013, 35257483). ClinVar contains an entry for this variant (Variation ID: 212543). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;D;.;D;D;.;D;.;D;D;D;D;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaRNN	Benign	0.019	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Pathogenic	4.1	.;.;.;H;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.5	D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;D;.;D;.;D;D;D;D;.
Vest4		0.83
MVP		0.95
MPC		0.21, 0.34, 0.53, 0.52, 0.69, 0.21, 0.20, 0.56
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.93
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs34946978; hg19: chr2-234676872; COSMIC: COSV59380860; COSMIC: COSV59380860;