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_001040142.2(SCN2A):c.3007C>A (p.Leu1003Ile)

CA122775

12881 (ClinVar)

Gene: SCN2A
Condition: complex neurodevelopmental disorder
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 12afe231-b4eb-4d58-9a00-5ab7e3098777
Approved on: 2024-10-22
Published on: 2024-12-19

HGVS expressions

NM_001040142.2:c.3007C>A
NM_001040142.2(SCN2A):c.3007C>A (p.Leu1003Ile)
NC_000002.12:g.165354279C>A
CM000664.2:g.165354279C>A
NC_000002.11:g.166210789C>A
CM000664.1:g.166210789C>A
NC_000002.10:g.165919035C>A
NG_008143.1:g.119878C>A
ENST00000631182.3:c.3007C>A
ENST00000375437.7:c.3007C>A
ENST00000636071.2:c.3007C>A
ENST00000636135.1:c.*1326C>A
ENST00000636384.2:c.*994C>A
ENST00000636662.2:c.*3530C>A
ENST00000636769.1:c.*949C>A
ENST00000636985.2:c.2611C>A
ENST00000637266.2:c.3007C>A
ENST00000673831.1:c.753C>A
ENST00000673883.1:c.572C>A
ENST00000674133.1:c.858C>A
ENST00000283256.10:c.3007C>A
ENST00000375427.4:c.3007C>A
ENST00000375437.6:c.3007C>A
ENST00000480032.4:n.3150C>A
ENST00000631182.2:c.3007C>A
NM_001040142.1:c.3007C>A
NM_001040143.1:c.3007C>A
NM_021007.2:c.3007C>A
NM_001040143.2:c.3007C>A
NM_001371246.1:c.3007C>A
NM_001371247.1:c.3007C>A
NM_021007.3:c.3007C>A
More

Uncertain Significance

Met criteria codes 2
PS4_Supporting PM2_Supporting
Not Met criteria codes 16
BP2 BP4 BP5 PS2 PS3 PS1 PP1 PP3 PM6 PM5 PM1 BA1 BS2 BS4 BS3 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN2A Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Epilepsy Sodium Channel VCEP
The NM_001040142.2(SCN2A):c.3007C>A (p.Leu1003Ile) variant in SCN2A is a missense variant predicted to cause substitution of leucine by isoleucine at amino acid 1003 (p.Leu1003Ile). This variant has been reported in one family meeting phenotypic criteria for Complex Neurodevelopmental Disorder (MONDO:0100038 (PS4_Supporting; PMID 15048894). In this family, the variant was reported to segregate with Complex Neurodevelopmental Disorder (MONDO:0100038) in two meioses (father with two affected children). This does not meet the threshold of three meioses to apply PP1 (PMID 15048894). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Complex Neurodevelopmental Disorder (MONDO:0100038) based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: PM2_Supporting, PS4_Supporting. (ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN2A Version 1.0.0; approved 10/22/2024).
Met criteria codes
PS4_Supporting
This variant has been reported in 1 family meeting phenotypic criteria for Complex Neurodevelopmental Disorder (MONDO:0100038) (PS4_Supporting; PMID 15048894).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
Not Met criteria codes
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
The computational predictor REVEL gives a score of 0.643, which is neither above nor below the thresholds predicting a damaging or benign impact on SCN2A function.
BP5
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
To our knowledge, functional assays have not been reported for this variant.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
The variant has been reported to segregate with Complex Neurodevelopmental Disorder (MONDO:0100038) in 2 meioses from 1 family (father with 2 affected children). This does not meet the threshold of 3 meioses to apply PP1 (PMID 15048894).
PP3
The computational predictor REVEL gives a score of 0.643, which is neither above nor below the thresholds predicting a damaging or benign impact on SCN2A function.
PM6
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
PM1
This variant does not reside within a region of SCN2A that is defined as a mutational hotspot or critical functional domain by the ClinGen Epilepsy Sodium Channel VCEP.
BA1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
To our knowledge, functional assays have not been reported for this variant.
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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