Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000023.4(SGCA):c.1153_1163del (p.Asp385fs)

CA626689324

594086 (ClinVar)

Gene: SGCA
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: c924ff25-ac92-4b0f-ad14-3a0ca1424d50
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_000023.4:c.1153_1163del
NM_000023.4(SGCA):c.1153_1163del (p.Asp385fs)
NC_000017.11:g.50175426_50175436del
CM000679.2:g.50175426_50175436del
NC_000017.10:g.48252787_48252797del
CM000679.1:g.48252787_48252797del
NC_000017.9:g.45607786_45607796del
NG_008889.1:g.14422_14432del
ENST00000504307.3:n.547-3256_547-3246del
ENST00000504073.2:c.1003_1013del
ENST00000504307.2:n.492-3256_492-3246del
ENST00000511303.6:n.455+51_455+61del
ENST00000682109.1:c.1033_1043del
ENST00000683226.1:n.1751_1761del
ENST00000683294.1:c.*256_*266del
ENST00000683544.1:n.807_817del
ENST00000262018.8:c.1153_1163del
ENST00000262018.7:c.1153_1163del
ENST00000344627.10:c.781_791del
ENST00000504073.1:c.470_480del
ENST00000504307.1:n.470-3256_470-3246del
ENST00000505964.1:n.254_264del
ENST00000508382.1:n.198_208del
ENST00000511303.5:c.451+51_451+61del
ENST00000513821.5:c.*47_*57del
ENST00000513942.5:n.572_582del
NM_000023.2:c.1153_1163del
NM_001135697.1:c.781_791del
NM_000023.3:c.1153_1163del
NM_001135697.2:c.781_791del
NR_135553.1:n.1000_1010del
NM_001135697.3:c.781_791del
NR_135553.2:n.980_990del
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Uncertain Significance

Met criteria codes 2
PVS1_Moderate PM2_Supporting
Not Met criteria codes 21
BS4 BS3 BS1 BS2 PS4 PS2 PS3 PS1 BP5 BP7 BP4 BP1 BP2 BP3 BA1 PP3 PP2 PM6 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCA Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_000023.4: c.1153_1163del p.(Asp385ThrfsTer3) variant in SGCA is expected to cause a frameshift of the last four amino acids of the protein without premature truncation, which may disrupt the function of the protein; however, the resulting transcript is predicted to escape nonsense mediated decay (PVS1_Moderate). The highest population minor allele frequency of this variant is 0.00006 (1/15750 alleles) in the African/African American population in gnomAD v2.1.1, which is less than the ClinGen LGMD VCEP threshold (0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant cannot be classified as pathogenic nor benign at this time and remains a variant of uncertain significance for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/07/2025): PVS1_Moderate, PM2_Supporting.
Met criteria codes
PVS1_Moderate
The NM_000023.4:c.1153_1163del (p.Asp385fs) variant in SGCA is a frameshift variant that may cause loss of function of the protein; however, it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate).
PM2_Supporting
The highest population minor allele frequency for this variant is 0.00006 (1/15750 alleles) in the African/African American population in gnomAD v2.1.1, which is less than the ClinGen LGMD VCEP threshold (0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting).
Not Met criteria codes
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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