rs199422295
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_198253.3(TERT):c.2045G>A(p.Gly682Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G682R) has been classified as Uncertain significance.
Frequency
Consequence
NM_198253.3 missense
Scores
Clinical Significance
Conservation
Publications
- pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- dyskeratosis congenita, autosomal dominant 2Inheritance: AR, AD, SD, Unknown Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
- acute myeloid leukemiaInheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- dyskeratosis congenitaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Hoyeraal-Hreidarsson syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- melanoma, cutaneous malignant, susceptibility to, 9Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2045G>A | p.Gly682Asp | missense_variant | Exon 5 of 16 | ENST00000310581.10 | NP_937983.2 | |
TERT | NM_001193376.3 | c.2045G>A | p.Gly682Asp | missense_variant | Exon 5 of 15 | NP_001180305.1 | ||
TERT | NR_149162.3 | n.2124G>A | non_coding_transcript_exon_variant | Exon 5 of 13 | ||||
TERT | NR_149163.3 | n.2124G>A | non_coding_transcript_exon_variant | Exon 5 of 13 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.00 AC: 0AN: 167544 AF XY: 0.00
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1413070Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 698768
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal dominant 1 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at