NM_177438.3(DICER1):c.3764G>T (p.Ser1255Ile) AND DICER1-related tumor predisposition

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 8, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003029140.3

Allele description [Variation Report for NM_177438.3(DICER1):c.3764G>T (p.Ser1255Ile)]

NM_177438.3(DICER1):c.3764G>T (p.Ser1255Ile)

Gene:

DICER1:dicer 1, ribonuclease III [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_177438.3(DICER1):c.3764G>T (p.Ser1255Ile)

HGVS:

NC_000014.9:g.95103632C>A
NG_016311.1:g.58791G>T
NM_001195573.1:c.3764G>T
NM_001271282.3:c.3764G>T
NM_001291628.2:c.3764G>T
NM_001395677.1:c.3764G>T
NM_001395678.1:c.3764G>T
NM_001395679.1:c.3764G>T
NM_001395680.1:c.3764G>T
NM_001395681.1:c.3764G>T
NM_001395682.1:c.3764G>T
NM_001395683.1:c.3764G>T
NM_001395684.1:c.3764G>T
NM_001395686.1:c.3482G>T
NM_001395687.1:c.3359G>T
NM_001395688.1:c.3359G>T
NM_001395689.1:c.3359G>T
NM_001395690.1:c.3359G>T
NM_001395691.1:c.3197G>T
NM_001395692.1:c.3764G>T
NM_001395693.1:c.3764G>T
NM_001395694.1:c.3764G>T
NM_001395695.1:c.3764G>T
NM_001395696.1:c.3359G>T
NM_001395697.1:c.2081G>T
NM_030621.4:c.3764G>T
NM_177438.3:c.3764G>TMANE SELECT
NP_001182502.1:p.Ser1255Ile
NP_001258211.1:p.Ser1255Ile
NP_001278557.1:p.Ser1255Ile
NP_001382606.1:p.Ser1255Ile
NP_001382607.1:p.Ser1255Ile
NP_001382608.1:p.Ser1255Ile
NP_001382609.1:p.Ser1255Ile
NP_001382610.1:p.Ser1255Ile
NP_001382611.1:p.Ser1255Ile
NP_001382612.1:p.Ser1255Ile
NP_001382613.1:p.Ser1255Ile
NP_001382615.1:p.Ser1161Ile
NP_001382616.1:p.Ser1120Ile
NP_001382617.1:p.Ser1120Ile
NP_001382618.1:p.Ser1120Ile
NP_001382619.1:p.Ser1120Ile
NP_001382620.1:p.Ser1066Ile
NP_001382621.1:p.Ser1255Ile
NP_001382622.1:p.Ser1255Ile
NP_001382623.1:p.Ser1255Ile
NP_001382624.1:p.Ser1255Ile
NP_001382625.1:p.Ser1120Ile
NP_001382626.1:p.Ser694Ile
NP_085124.2:p.Ser1255Ile
NP_803187.1:p.Ser1255Ile
NP_803187.1:p.Ser1255Ile
LRG_492t1:c.3764G>T
LRG_492:g.58791G>T
LRG_492p1:p.Ser1255Ile
NC_000014.8:g.95569969C>A
NM_177438.2:c.3764G>T
NR_172715.1:n.4182G>T
NR_172716.1:n.4366G>T
NR_172717.1:n.4276G>T
NR_172718.1:n.4199G>T
NR_172719.1:n.4032G>T
NR_172720.1:n.4109G>T

Protein change:

S1066I

Molecular consequence:

NM_001195573.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001271282.3:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001291628.2:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395677.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395678.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395679.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395680.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395681.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395682.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395683.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395684.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395686.1:c.3482G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395687.1:c.3359G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395688.1:c.3359G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395689.1:c.3359G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395690.1:c.3359G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395691.1:c.3197G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395692.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395693.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395694.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395695.1:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395696.1:c.3359G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001395697.1:c.2081G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_030621.4:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_177438.3:c.3764G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_172715.1:n.4182G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_172716.1:n.4366G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_172717.1:n.4276G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_172718.1:n.4199G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_172719.1:n.4032G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_172720.1:n.4109G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: DICER1-related tumor predisposition
Synonyms:: DICER1-related pleuropulmonary blastoma cancer predisposition syndrome; DICER1 syndrome
Identifiers:: MONDO: MONDO:0100216; MedGen: C3839822

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003326616	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003326616

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003326616.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1255 of the DICER1 protein (p.Ser1255Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2107299). 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 not expected to disrupt DICER1 protein function with a negative predictive value of 80%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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Relating variation to medicine