14-24097012-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004563.4(PCK2):c.150C>T(p.His50His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
PCK2
NM_004563.4 synonymous
NM_004563.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.195
Genes affected
PCK2 (HGNC:8725): (phosphoenolpyruvate carboxykinase 2, mitochondrial) This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2014]
NRL (HGNC:8002): (neural retina leucine zipper) This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 14-24097012-C-T is Benign according to our data. Variant chr14-24097012-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1634621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.195 with no splicing effect.
BS2
High AC in GnomAdExome4 at 115 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCK2 | NM_004563.4 | c.150C>T | p.His50His | synonymous_variant | Exon 2 of 10 | ENST00000216780.9 | NP_004554.3 | |
NRL | NM_001354768.3 | c.-27-14137G>A | intron_variant | Intron 1 of 2 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCK2 | ENST00000216780.9 | c.150C>T | p.His50His | synonymous_variant | Exon 2 of 10 | 1 | NM_004563.4 | ENSP00000216780.4 | ||
NRL | ENST00000561028.6 | c.-27-14137G>A | intron_variant | Intron 1 of 2 | 2 | NM_001354768.3 | ENSP00000454062.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151864Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251212Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135820
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GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461796Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727200
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151864Hom.: 0 Cov.: 30 AF XY: 0.0000405 AC XY: 3AN XY: 74154
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Dec 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
PCK2: BP4, BP7 -
Oct 25, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at