NM_000939.4(POMC):c.599_604dup (p.Ala201_Gln202insArgAla) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000487385.5

Allele description [Variation Report for NM_000939.4(POMC):c.599_604dup (p.Ala201_Gln202insArgAla)]

NM_000939.4(POMC):c.599_604dup (p.Ala201_Gln202insArgAla)

Gene:

POMC:proopiomelanocortin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_000939.4(POMC):c.599_604dup (p.Ala201_Gln202insArgAla)

HGVS:

NC_000002.12:g.25161281_25161286dup
NG_008997.1:g.12405_12410dup
NM_000939.4:c.599_604dupMANE SELECT
NM_001035256.3:c.599_604dup
NM_001319204.2:c.599_604dup
NM_001319205.2:c.599_604dup
NP_000930.1:p.Ala201_Gln202insArgAla
NP_001030333.1:p.Ala201_Gln202insArgAla
NP_001306133.1:p.Ala201_Gln202insArgAla
NP_001306134.1:p.Ala201_Gln202insArgAla
NC_000002.11:g.25384149_25384150insGGGCCC
NC_000002.11:g.25384150_25384155dup
NM_001035256.1:c.599_604dup
NM_001035256.1:c.599_604dupGGGCCC

Links:

dbSNP: rs762710034

NCBI 1000 Genomes Browser:

rs762710034

Molecular consequence:

NM_000939.4:c.599_604dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001035256.3:c.599_604dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001319204.2:c.599_604dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001319205.2:c.599_604dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

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
SCV000568824	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Nov 29, 2016)	germline	clinical testing	Citation Link,
SCV002213309	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9768693, 29970488, 35574020, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568824

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Nov 29, 2016)

germline

clinical testing

Citation Link,

SCV002213309

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes.

Hinney A, Becker I, Heibült O, Nottebom K, Schmidt A, Ziegler A, Mayer H, Siegfried W, Blum WF, Remschmidt H, Hebebrand J.

J Clin Endocrinol Metab. 1998 Oct;83(10):3737-41.

PubMed [citation]

PMID:: 9768693

Genetic obesity: next-generation sequencing results of 1230 patients with obesity.

Kleinendorst L, Massink MPG, Cooiman MI, Savas M, van der Baan-Slootweg OH, Roelants RJ, Janssen ICM, Meijers-Heijboer HJ, Knoers NVAM, Ploos van Amstel HK, van Rossum EFC, van den Akker ELT, van Haaften G, van der Zwaag B, van Haelst MM.

J Med Genet. 2018 Sep;55(9):578-586. doi: 10.1136/jmedgenet-2018-105315. Epub 2018 Jul 3.

PubMed [citation]

PMID:: 29970488

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000568824.4

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

Description

The c.599_604dupGGGCCC variant in the POMC gene has been reported previously, according to alternate nomeclature, in cis with a nonsense variant (E206X) and in trans with a missense variant (E214G), in a German adolescent female with obesity (Hinney et al., 1998). The c.599_604dupGGGCCC variant results in an in-frame insertion of two residues, an Arginine and an Alanine, at position 202 in the protein, denoted p.Ala201_Gln202insArgAla. The c.599_604dupGGGCCC variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, we interpret c.599_604dupGGGCCC as a variant of uncertain significance.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002213309.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant, c.599_604dup, results in the insertion of 2 amino acid(s) of the POMC protein (p.Ala201_Gln202insArgAla), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs762710034, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with obesity, in cis with a nearby nonsense variant (PMID: 9768693, 29970488, 35574020). ClinVar contains an entry for this variant (Variation ID: 420163). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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