ClinVar Miner

Submissions for variant NM_006412.4(AGPAT2):c.646A>T (p.Lys216Ter)

gnomAD frequency: 0.00103  dbSNP: rs138994150
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000880987 SCV001024123 likely benign not provided 2018-10-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000412630 SCV001752549 likely pathogenic Congenital generalized lipodystrophy type 1 2021-06-30 criteria provided, single submitter clinical testing
Mendelics RCV000412630 SCV002517536 pathogenic Congenital generalized lipodystrophy type 1 2022-05-04 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000412630 SCV004175790 likely pathogenic Congenital generalized lipodystrophy type 1 2023-02-14 criteria provided, single submitter clinical testing The stop gained c.646A>T(p.Lys216Ter) variant in AGPAT2 gene has been reported previously in homozygous state in individual(s) affected with Berardinelli-Seip congenital lipodystrophy (Akinci B, et. al.,2016; Magré J, et. al., 2003). The c.646A>T variant has been reported with allele frequency of 0.04% in gnomAD Exomes databases. This variant has been reported to the ClinVar database as Likely Benign/ Uncertain Significance / Likely Pathogenic / Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000412630 SCV005920892 likely pathogenic Congenital generalized lipodystrophy type 1 2023-05-10 criteria provided, single submitter research
GeneReviews RCV000412630 SCV000490124 not provided Congenital generalized lipodystrophy type 1 no assertion provided literature only
PreventionGenetics, part of Exact Sciences RCV004751505 SCV005358239 likely pathogenic AGPAT2-related disorder 2024-03-25 no assertion criteria provided clinical testing The AGPAT2 c.646A>T variant is predicted to result in premature protein termination (p.Lys216*). This variant has been reported in multiple individuals with Berardinelli-Seip lipodystrophy in the homozygous state (Magre et al 2003. PubMed ID: 12765973; Akinci et al 2016. PubMed ID: 27144933; Guo et al 2020. PubMed ID: 32800040; Costa-Riuetto et al. 2020 PubMed: 34033296; Saydam et al. 2021. PubMed: 34593051). This variant is reported in 0.33% of alleles in individuals of African descent in gnomAD. Nonsense variants in AGPAT2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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