Variant 11-117820666-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001680.5(FXYD2):c.*6G>T variant causes a splice region, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FXYD2
NM_001680.5 splice_region, 3_prime_UTR

Scores

Splicing: ADA: 0.9993

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.60

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]

FXYD2 links:

FXYD6-FXYD2 (HGNC:):

FXYD6-FXYD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 11-117820666-C-A is Benign according to our data. Variant chr11-117820666-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053963.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 141 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
FXYD2	NM_001680.5 linkuse as main transcript	c.*6G>T	splice_region_variant, 3_prime_UTR_variant	5/6	ENST00000292079.7
FXYD6-FXYD2	NM_001243598.4 linkuse as main transcript	c.*40G>T	splice_region_variant, 3_prime_UTR_variant	9/10
FXYD6-FXYD2	NM_001204268.3 linkuse as main transcript	c.*6G>T	splice_region_variant, 3_prime_UTR_variant	10/11
FXYD2	NM_021603.4 linkuse as main transcript	c.*6G>T	splice_region_variant, 3_prime_UTR_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000292079.7 linkuse as main transcript	c.*6G>T		splice_region_variant, 3_prime_UTR_variant	5/6	1	NM_001680.5		P54710-1
	ENST00000531850.2 linkuse as main transcript	n.482C>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.000927

AC:

141

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000259

AC:

AN:

251066

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00376

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

146

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00400

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000926

AC:

141

AN:

152292

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000173

Hom.:

Bravo

AF:

0.00110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FXYD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.91

SpliceAI score (max)

0.81

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.81

Position offset: 0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over