chr11-117820678-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001680.5(FXYD2):c.195G>A(p.Glu65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,614,038 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 7 hom., cov: 31)
Exomes 𝑓: 0.0065 ( 90 hom. )
Consequence
FXYD2
NM_001680.5 synonymous
NM_001680.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.50
Genes affected
FXYD2 (HGNC:4026): (FXYD domain containing ion transport regulator 2) This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes the sodium/potassium-transporting ATPase subunit gamma. Mutations in this gene have been associated with Renal Hypomagnesemia-2. Alternatively spliced transcript variants have been described. Read-through transcripts have been observed between this locus and the upstream FXYD domain-containing ion transport regulator 6 (FXYD6, GeneID 53826) locus.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-117820678-C-T is Benign according to our data. Variant chr11-117820678-C-T is described in ClinVar as [Benign]. Clinvar id is 302522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00418 (636/152276) while in subpopulation SAS AF= 0.0195 (94/4826). AF 95% confidence interval is 0.0163. There are 7 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 636 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FXYD2 | NM_001680.5 | c.195G>A | p.Glu65= | synonymous_variant | 5/6 | ENST00000292079.7 | |
FXYD6-FXYD2 | NM_001243598.4 | c.*28G>A | 3_prime_UTR_variant | 9/10 | |||
FXYD6-FXYD2 | NM_001204268.3 | c.429G>A | p.Glu143= | synonymous_variant | 10/11 | ||
FXYD2 | NM_021603.4 | c.189G>A | p.Glu63= | synonymous_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FXYD2 | ENST00000292079.7 | c.195G>A | p.Glu65= | synonymous_variant | 5/6 | 1 | NM_001680.5 | ||
ENST00000531850.2 | n.494C>T | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00419 AC: 637AN: 152158Hom.: 7 Cov.: 31
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GnomAD3 exomes AF: 0.00682 AC: 1712AN: 251096Hom.: 26 AF XY: 0.00779 AC XY: 1058AN XY: 135748
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GnomAD4 exome AF: 0.00650 AC: 9496AN: 1461762Hom.: 90 Cov.: 33 AF XY: 0.00695 AC XY: 5054AN XY: 727186
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GnomAD4 genome AF: 0.00418 AC: 636AN: 152276Hom.: 7 Cov.: 31 AF XY: 0.00418 AC XY: 311AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | - - |
Renal hypomagnesemia 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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