NM_006734.4:c.6475G>C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_006734.4(HIVEP2):āc.6475G>Cā(p.Gly2159Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,460,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006734.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248328Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134726
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460548Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726632
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 43 Uncertain:1
The observed missense c.6475G>C (p.Gly2159Arg) variant in HIVEP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Another variant on the same codon [c.6475G>T, p.Gly2159X] of HIVEP2 gene has been reported previously in an individual affected with developmental delay, intellectual disabilities, and mild dysmorphic features (Steinfeld et al., 2016). The p.Gly2159Arg variant is present with allele frequency of 0.002% in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (Polyphen - Probably Damaging, SIFT - Tolerated and MutationTaster - Disease Causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Gly2159Arg in HIVEP2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 2159 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at