NM_021951.3(DMRT1):c.671A>G (p.Asn224Ser) AND not provided

Clinical significance:Benign/Likely benign (Last evaluated: Aug 20, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000235005.4

Allele description [Variation Report for NM_021951.3(DMRT1):c.671A>G (p.Asn224Ser)]

NM_021951.3(DMRT1):c.671A>G (p.Asn224Ser)

Gene:
DMRT1:doublesex and mab-3 related transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9p24.3
Genomic location:
Preferred name:
NM_021951.3(DMRT1):c.671A>G (p.Asn224Ser)
Other names:
DMRT1, ASN224SER (rs140506267)
HGVS:
  • NC_000009.12:g.894044A>G
  • NG_009221.1:g.57355A>G
  • NM_001363767.1:c.197A>G
  • NM_021951.3:c.671A>GMANE SELECT
  • NP_001350696.1:p.Asn66Ser
  • NP_068770.2:p.Asn224Ser
  • NC_000009.11:g.894044A>G
  • NM_021951.2:c.671A>G
Protein change:
N224S; ASN224SER
Links:
OMIM: 602424.0001; dbSNP: rs140506267
NCBI 1000 Genomes Browser:
rs140506267
Molecular consequence:
  • NM_001363767.1:c.197A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021951.3:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000292373OMIMno assertion criteria providedUncertain significance
(Sep 11, 2018)
germlineliterature only

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

SCV001155587CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Likely benign
(Jan 1, 2018)
germlineclinical testing

Citation Link,

SCV001732499Invitaecriteria provided, single submitter
Benign
(Aug 20, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

DMRT1 mutations are rarely associated with male infertility.

Tewes AC, Ledig S, Tüttelmann F, Kliesch S, Wieacker P.

Fertil Steril. 2014 Sep;102(3):816-820.e3. doi: 10.1016/j.fertnstert.2014.05.022. Epub 2014 Jun 14.

PubMed [citation]
PMID:
24934491

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From OMIM, SCV000292373.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

This variant is classified as a variant of unknown significance because its contribution to spermatogenic failure (see 258150) has not been confirmed.

In 2 unrelated azoospermic men with complete bilateral Sertoli cell-only syndrome and decreased testicular volume by ultrasound, Tewes et al. (2014) identified heterozygosity for a c.671A-G transition in exon 3 of the DMRT1 gene, resulting in an asn224-to-ser (N224S) substitution. Both azoospermic men had decreased testosterone concentrations, and in 1 man, luteinizing hormone (LH; see 152780) and follicle-stimulating hormone (FSH; see 136530) were both elevated, whereas in the other man, only FSH was elevated. The mutation was not found in 215 normozoospermic controls, but was found in 0.46% of European Americans and in 0.046% of African Americans in the Exome Sequencing Project database. Tewes et al. (2014) stated that their results should be considered hypothesis-generating and not confirmatory, and suggested that DMRT1 single-base mutations may be rarely associated with male infertility.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001155587.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001732499.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 10, 2021

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