chr9-136673541-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_006412.4(AGPAT2):c.*211G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 462,394 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00046 ( 1 hom. )
Consequence
AGPAT2
NM_006412.4 3_prime_UTR
NM_006412.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.74
Genes affected
AGPAT2 (HGNC:325): (1-acylglycerol-3-phosphate O-acyltransferase 2) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000464 (144/310098) while in subpopulation EAS AF= 0.00403 (92/22830). AF 95% confidence interval is 0.00336. There are 1 homozygotes in gnomad4_exome. There are 69 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| AGPAT2 | NM_006412.4 | c.*211G>A | 3_prime_UTR_variant | 6/6 | ENST00000371696.7 | ||
| AGPAT2 | NM_001012727.2 | c.*211G>A | 3_prime_UTR_variant | 5/5 | |||
| AGPAT2 | XM_047422636.1 | c.*211G>A | 3_prime_UTR_variant | 6/6 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AGPAT2 | ENST00000371696.7 | c.*211G>A | 3_prime_UTR_variant | 6/6 | 1 | NM_006412.4 | P1 | ||
| AGPAT2 | ENST00000371694.7 | c.*211G>A | 3_prime_UTR_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes 0.000217 AC: 33AN: 152178Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.000464 AC: 144AN: 310098Hom.: 1 Cov.: 5 AF XY: 0.000436 AC XY: 69AN XY: 158318
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GnomAD4 genome 0.000217 AC: 33AN: 152296Hom.: 0 Cov.: 34 AF XY: 0.000255 AC XY: 19AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital generalized lipodystrophy type 1 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at