NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 12, 2021
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:: RCV003098637.2

Allele description [Variation Report for NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu)]

NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu)

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu)

HGVS:

NC_000007.14:g.5982871G>T
NG_008466.1:g.31236C>A
NM_000535.7:c.2127C>AMANE SELECT
NM_001018040.1:c.1722C>A
NM_001322003.2:c.1722C>A
NM_001322004.2:c.1722C>A
NM_001322005.2:c.1722C>A
NM_001322006.2:c.1971C>A
NM_001322007.2:c.1809C>A
NM_001322008.2:c.1809C>A
NM_001322009.2:c.1722C>A
NM_001322010.2:c.1566C>A
NM_001322011.2:c.1194C>A
NM_001322012.2:c.1194C>A
NM_001322013.2:c.1554C>A
NM_001322014.2:c.2127C>A
NM_001322015.2:c.1818C>A
NM_001406866.1:c.2313C>A
NM_001406868.1:c.2151C>A
NM_001406869.1:c.2019C>A
NM_001406870.1:c.1971C>A
NM_001406871.1:c.2127C>A
NM_001406873.1:c.1929C>A
NM_001406874.1:c.1959C>A
NM_001406875.1:c.1818C>A
NM_001406876.1:c.1809C>A
NM_001406877.1:c.1818C>A
NM_001406878.1:c.1818C>A
NM_001406879.1:c.1818C>A
NM_001406880.1:c.1818C>A
NM_001406881.1:c.1818C>A
NM_001406882.1:c.1818C>A
NM_001406883.1:c.1809C>A
NM_001406884.1:c.1803C>A
NM_001406885.1:c.1791C>A
NM_001406886.1:c.1761C>A
NM_001406887.1:c.1722C>A
NM_001406888.1:c.1722C>A
NM_001406889.1:c.1722C>A
NM_001406890.1:c.1722C>A
NM_001406891.1:c.1722C>A
NM_001406892.1:c.1722C>A
NM_001406893.1:c.1722C>A
NM_001406894.1:c.1722C>A
NM_001406895.1:c.1722C>A
NM_001406896.1:c.1722C>A
NM_001406897.1:c.1722C>A
NM_001406898.1:c.1722C>A
NM_001406899.1:c.1722C>A
NM_001406900.1:c.1662C>A
NM_001406901.1:c.1653C>A
NM_001406902.1:c.1653C>A
NM_001406904.1:c.1614C>A
NM_001406905.1:c.1614C>A
NM_001406906.1:c.1566C>A
NM_001406907.1:c.1566C>A
NM_001406909.1:c.1554C>A
NM_001406911.1:c.1356C>A
NM_001406912.1:c.924C>A
NP_000526.1:p.Phe709Leu
NP_000526.2:p.Phe709Leu
NP_001018050.1:p.Phe574Leu
NP_001308932.1:p.Phe574Leu
NP_001308933.1:p.Phe574Leu
NP_001308934.1:p.Phe574Leu
NP_001308935.1:p.Phe657Leu
NP_001308936.1:p.Phe603Leu
NP_001308937.1:p.Phe603Leu
NP_001308938.1:p.Phe574Leu
NP_001308939.1:p.Phe522Leu
NP_001308940.1:p.Phe398Leu
NP_001308941.1:p.Phe398Leu
NP_001308942.1:p.Phe518Leu
NP_001308943.1:p.Phe709Leu
NP_001308944.1:p.Phe606Leu
NP_001393795.1:p.Phe771Leu
NP_001393797.1:p.Phe717Leu
NP_001393798.1:p.Phe673Leu
NP_001393799.1:p.Phe657Leu
NP_001393800.1:p.Phe709Leu
NP_001393802.1:p.Phe643Leu
NP_001393803.1:p.Phe653Leu
NP_001393804.1:p.Phe606Leu
NP_001393805.1:p.Phe603Leu
NP_001393806.1:p.Phe606Leu
NP_001393807.1:p.Phe606Leu
NP_001393808.1:p.Phe606Leu
NP_001393809.1:p.Phe606Leu
NP_001393810.1:p.Phe606Leu
NP_001393811.1:p.Phe606Leu
NP_001393812.1:p.Phe603Leu
NP_001393813.1:p.Phe601Leu
NP_001393814.1:p.Phe597Leu
NP_001393815.1:p.Phe587Leu
NP_001393816.1:p.Phe574Leu
NP_001393817.1:p.Phe574Leu
NP_001393818.1:p.Phe574Leu
NP_001393819.1:p.Phe574Leu
NP_001393820.1:p.Phe574Leu
NP_001393821.1:p.Phe574Leu
NP_001393822.1:p.Phe574Leu
NP_001393823.1:p.Phe574Leu
NP_001393824.1:p.Phe574Leu
NP_001393825.1:p.Phe574Leu
NP_001393826.1:p.Phe574Leu
NP_001393827.1:p.Phe574Leu
NP_001393828.1:p.Phe574Leu
NP_001393829.1:p.Phe554Leu
NP_001393830.1:p.Phe551Leu
NP_001393831.1:p.Phe551Leu
NP_001393833.1:p.Phe538Leu
NP_001393834.1:p.Phe538Leu
NP_001393835.1:p.Phe522Leu
NP_001393836.1:p.Phe522Leu
NP_001393838.1:p.Phe518Leu
NP_001393840.1:p.Phe452Leu
NP_001393841.1:p.Phe308Leu
LRG_161t1:c.2127C>A
LRG_161:g.31236C>A
LRG_161p1:p.Phe709Leu
NC_000007.13:g.6022502G>T
NM_000535.5:c.2127C>A
NR_003085.2:n.2209C>A
NR_136154.1:n.2214C>A

Protein change:

F308L

Molecular consequence:

NM_000535.7:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001018040.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1971C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1194C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1194C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1554C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406866.1:c.2313C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406868.1:c.2151C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406869.1:c.2019C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406870.1:c.1971C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406871.1:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406873.1:c.1929C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406874.1:c.1959C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406875.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406876.1:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406877.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406878.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406879.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406880.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406881.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406882.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406883.1:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406884.1:c.1803C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406885.1:c.1791C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406886.1:c.1761C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406887.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406888.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406889.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406890.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406891.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406892.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406893.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406894.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406895.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406896.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406897.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406898.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406899.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406900.1:c.1662C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406901.1:c.1653C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406902.1:c.1653C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406904.1:c.1614C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406905.1:c.1614C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406906.1:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406907.1:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406909.1:c.1554C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406911.1:c.1356C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406912.1:c.924C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2214C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

Clear Turn Off Turn On

Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 8, ZJU1.0, whole genom...
Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 8, ZJU1.0, whole genome shotgun sequence
gi|1938545151|gnl|ASM:GCF_015476395 |ref|NC_051779.1||gpp|GPC_000008887.1||gnl|NCBI_GENOMES|97774

Nucleotide
Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 33, whole genome shotg...
Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 33, whole genome shotgun sequence
gi|1935523722|gb|CM027274.1||gnl|WG GAL|chr33

Nucleotide
Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 6, whole genome shotgu...
Anas platyrhynchos isolate Z2 breed Pekin duck chromosome 6, whole genome shotgun sequence
gi|1935523748|gb|CM027248.1||gnl|WG GAL|chr6

Nucleotide
26S proteasome regulatory subunit 6A [Homo sapiens]
26S proteasome regulatory subunit 6A [Homo sapiens]
gi|21361144|ref|NP_002795.2|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003243121	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2021)	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

SCV003243121

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 12, 2021)

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, SCV003243121.1

#	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 phenylalanine with leucine at codon 709 of the PMS2 protein (p.Phe709Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Sep 29, 2024

ClinVar

Relating variation to medicine