X-44178494-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000420999.2(EFHC2):c.1822C>T(p.Arg608Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,092,492 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R608H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000420999.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EFHC2 | NM_025184.4 | c.1822C>T | p.Arg608Cys | missense_variant | 12/15 | ENST00000420999.2 | NP_079460.2 | |
EFHC2 | XM_047442535.1 | c.1822C>T | p.Arg608Cys | missense_variant | 12/14 | XP_047298491.1 | ||
EFHC2 | XM_047442536.1 | c.1822C>T | p.Arg608Cys | missense_variant | 12/15 | XP_047298492.1 | ||
EFHC2 | XM_006724562.3 | c.1234C>T | p.Arg412Cys | missense_variant | 11/14 | XP_006724625.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EFHC2 | ENST00000420999.2 | c.1822C>T | p.Arg608Cys | missense_variant | 12/15 | 1 | NM_025184.4 | ENSP00000404232 | P1 | |
EFHC2 | ENST00000343571.3 | n.143C>T | non_coding_transcript_exon_variant | 2/5 | 2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 exomes AF: 0.0000347 AC: 6AN: 172945Hom.: 0 AF XY: 0.0000335 AC XY: 2AN XY: 59783
GnomAD4 exome AF: 0.0000330 AC: 36AN: 1092492Hom.: 0 Cov.: 30 AF XY: 0.0000195 AC XY: 7AN XY: 358392
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2023 | The c.1822C>T (p.R608C) alteration is located in exon 12 (coding exon 12) of the EFHC2 gene. This alteration results from a C to T substitution at nucleotide position 1822, causing the arginine (R) at amino acid position 608 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at