11-117820203-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001680.5(FXYD2):​c.*176T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 167,860 control chromosomes in the GnomAD database, including 7,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6588 hom., cov: 32)
Exomes 𝑓: 0.33 ( 950 hom. )

Consequence

FXYD2
NM_001680.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.289
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 11-117820203-A-C is Benign according to our data. Variant chr11-117820203-A-C is described in ClinVar as [Benign]. Clinvar id is 302515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FXYD2NM_001680.5 linkuse as main transcriptc.*176T>G 3_prime_UTR_variant 6/6 ENST00000292079.7
FXYD6-FXYD2NM_001243598.4 linkuse as main transcriptc.*210T>G 3_prime_UTR_variant 10/10
FXYD6-FXYD2NM_001204268.3 linkuse as main transcriptc.*176T>G 3_prime_UTR_variant 11/11
FXYD2NM_021603.4 linkuse as main transcriptc.*176T>G 3_prime_UTR_variant 6/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FXYD2ENST00000292079.7 linkuse as main transcriptc.*176T>G 3_prime_UTR_variant 6/61 NM_001680.5 P54710-1
ENST00000531850.2 linkuse as main transcriptn.277-258A>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.276
AC:
41931
AN:
151986
Hom.:
6588
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.150
Gnomad AMI
AF:
0.293
Gnomad AMR
AF:
0.306
Gnomad ASJ
AF:
0.333
Gnomad EAS
AF:
0.0955
Gnomad SAS
AF:
0.167
Gnomad FIN
AF:
0.319
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.357
Gnomad OTH
AF:
0.279
GnomAD4 exome
AF:
0.329
AC:
5183
AN:
15756
Hom.:
950
Cov.:
0
AF XY:
0.327
AC XY:
2617
AN XY:
8014
show subpopulations
Gnomad4 AFR exome
AF:
0.148
Gnomad4 AMR exome
AF:
0.380
Gnomad4 ASJ exome
AF:
0.377
Gnomad4 EAS exome
AF:
0.0845
Gnomad4 SAS exome
AF:
0.178
Gnomad4 FIN exome
AF:
0.310
Gnomad4 NFE exome
AF:
0.359
Gnomad4 OTH exome
AF:
0.329
GnomAD4 genome
AF:
0.276
AC:
41935
AN:
152104
Hom.:
6588
Cov.:
32
AF XY:
0.267
AC XY:
19871
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.149
Gnomad4 AMR
AF:
0.306
Gnomad4 ASJ
AF:
0.333
Gnomad4 EAS
AF:
0.0951
Gnomad4 SAS
AF:
0.168
Gnomad4 FIN
AF:
0.319
Gnomad4 NFE
AF:
0.357
Gnomad4 OTH
AF:
0.276
Alfa
AF:
0.343
Hom.:
13543
Bravo
AF:
0.273

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Renal hypomagnesemia 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.9
DANN
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11999; hg19: chr11-117690918; API