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_001083962.2(TCF4):c.1990G>A (p.Ala664Thr)

CA319091

207527 (ClinVar)

Gene: TCF4
Condition: Pitt-Hopkins syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e9bb91ba-79af-46e0-8fd4-35d9ec3eefa8
Approved on: 2024-08-30
Published on: 2024-12-13

HGVS expressions

NM_001083962.2:c.1990G>A
NM_001083962.2(TCF4):c.1990G>A (p.Ala664Thr)
NC_000018.10:g.55228251C>T
CM000680.2:g.55228251C>T
NC_000018.9:g.52895482C>T
CM000680.1:g.52895482C>T
NC_000018.8:g.51046480C>T
NG_011716.1:g.365379G>A
NG_011716.2:g.412743G>A
ENST00000354452.8:c.1990G>A
ENST00000635822.2:c.1870G>A
ENST00000635990.2:n.1670G>A
ENST00000636400.2:c.1918G>A
ENST00000636751.2:c.*1698G>A
ENST00000636822.2:c.1600G>A
ENST00000637115.2:c.*1868G>A
ENST00000637169.2:c.1342G>A
ENST00000637239.2:n.2045G>A
ENST00000637250.2:n.1684G>A
ENST00000637923.2:c.1588G>A
ENST00000638154.3:c.2017G>A
ENST00000643689.1:c.1600G>A
ENST00000674764.1:c.*1601G>A
ENST00000675707.1:c.1600G>A
ENST00000354452.7:c.1990G>A
ENST00000356073.8:c.1978G>A
ENST00000398339.5:c.2296G>A
ENST00000457482.7:c.1510G>A
ENST00000537578.5:c.1918G>A
ENST00000537856.7:c.1588G>A
ENST00000540999.5:c.1906G>A
ENST00000543082.5:c.1852G>A
ENST00000544241.6:c.1777G>A
ENST00000561831.7:c.1498G>A
ENST00000561992.5:c.1588G>A
ENST00000562680.5:n.5513G>A
ENST00000564228.5:c.1765G>A
ENST00000564403.6:c.2008G>A
ENST00000564999.5:c.1978G>A
ENST00000565018.6:c.1726G>A
ENST00000566279.5:c.1810G>A
ENST00000566286.5:c.1969G>A
ENST00000567880.5:c.1798G>A
ENST00000568673.5:c.1918G>A
ENST00000568740.5:c.1903G>A
ENST00000570177.6:c.1588G>A
ENST00000570287.6:c.1498G>A
ENST00000616053.4:c.1726G>A
ENST00000626584.2:c.1330G>A
ENST00000626631.1:c.220G>A
ENST00000629387.2:c.1990G>A
NM_001083962.1:c.1990G>A
NM_001243226.2:c.2296G>A
NM_001243227.1:c.1918G>A
NM_001243228.1:c.2008G>A
NM_001243230.1:c.1969G>A
NM_001243231.1:c.1852G>A
NM_001243232.1:c.1777G>A
NM_001243233.1:c.1588G>A
NM_001243234.1:c.1510G>A
NM_001243235.1:c.1498G>A
NM_001243236.1:c.1498G>A
NM_001306207.1:c.1906G>A
NM_001306208.1:c.1765G>A
NM_003199.2:c.1978G>A
NM_001330604.2:c.1987G>A
NM_001330605.2:c.1600G>A
NM_001348211.1:c.1864G>A
NM_001348212.1:c.1588G>A
NM_001348213.1:c.1600G>A
NM_001348214.1:c.1495G>A
NM_001348215.1:c.1342G>A
NM_001348216.1:c.1510G>A
NM_001348217.1:c.1918G>A
NM_001348218.1:c.1918G>A
NM_001348219.1:c.1906G>A
NM_001348220.1:c.1903G>A
NM_001243226.3:c.2296G>A
NM_001243227.2:c.1918G>A
NM_001243228.2:c.2008G>A
NM_001243231.2:c.1852G>A
NM_001243233.2:c.1588G>A
NM_001243234.2:c.1510G>A
NM_001243235.2:c.1498G>A
NM_001243236.2:c.1498G>A
NM_001330604.3:c.1987G>A
NM_001330605.3:c.1600G>A
NM_001348211.2:c.1864G>A
NM_001348212.2:c.1588G>A
NM_001348213.2:c.1600G>A
NM_001348214.2:c.1495G>A
NM_001348215.2:c.1342G>A
NM_001348216.2:c.1510G>A
NM_001348218.2:c.1918G>A
NM_001348219.2:c.1906G>A
NM_001369567.1:c.1990G>A
NM_001369568.1:c.1990G>A
NM_001369569.1:c.1987G>A
NM_001369570.1:c.1987G>A
NM_001369571.1:c.1978G>A
NM_001369572.1:c.1978G>A
NM_001369573.1:c.1975G>A
NM_001369574.1:c.1975G>A
NM_001369575.1:c.1918G>A
NM_001369576.1:c.1915G>A
NM_001369577.1:c.1915G>A
NM_001369578.1:c.1915G>A
NM_001369579.1:c.1915G>A
NM_001369580.1:c.1915G>A
NM_001369581.1:c.1915G>A
NM_001369582.1:c.1906G>A
NM_001369583.1:c.1906G>A
NM_001369584.1:c.1903G>A
NM_001369585.1:c.1903G>A
NM_001369586.1:c.1921G>A
NM_003199.3:c.1978G>A
NM_001243230.2:c.1969G>A
More

Benign

Met criteria codes 4
BS2 BP4 BP5 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TCF4 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The highest population minor allele frequency of the p.Ala664Thr variant in TCF4 in gnomAD v4.1 is 0.007675 in the Amish population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0003) for BA1, and therefore meets this criterion (BA1). The p.Ala664Thr variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). Computational analysis prediction tools suggest that the p.Ala664Thr variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Ala664Thr variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5). In summary, the p.Ala664Thr variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP4, BP5). (TCF4 specification v.3; approved on 8/30/2024)
Met criteria codes
BS2
The p.Ala664Thr variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2).
BP4
Computational analysis prediction tools suggest that the p.Ala664Thr variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4).
BP5
The p.Ala664Thr variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5).
BA1
The highest population minor allele frequency of the p.Ala664Thr variant in TCF4 in gnomAD v4.1 is 0.007675 in the Amish population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0003) for BA1, and therefore meets this criterion (BA1).
Curation History
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