11-117820430-C-T

Position:

• chr11-117820430-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001680.5(FXYD2):​c.*7-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 571,224 control chromosomes in the GnomAD database, including 118,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27428 hom., cov: 31)
  • Exomes 𝑓: 0.65 (91495 hom.)
• Consequence: FXYD2 NM_001680.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.02

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]

FXYD6-FXYD2 (HGNC:39978): (FXYD6-FXYD2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FXYD domain-containing ion transport regulator 6 (GeneID 53826) and sodium/potassium-transporting ATPase subunit gamma (GeneID 486) genes on chromosome 11. One read-through transcript produces a fusion protein that shares sequence identity with each individual gene product, while another read-through transcript encodes a protein that has a distinct C-terminus and only shares sequence identity with the upstream locus (GeneID 53826). [provided by RefSeq, Aug 2011]

ENSG00000254844 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-117820430-C-T is Benign according to our data. Variant chr11-117820430-C-T is described in ClinVar as [Benign]. Clinvar id is 1243897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXYD2	NM_001680.5	c.*7-58G>A		intron_variant		ENST00000292079.7	NP_001671.2
FXYD6-FXYD2	NM_001204268.3	c.*7-58G>A		intron_variant			NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.*41-58G>A		intron_variant			NP_001230527.1
FXYD2	NM_021603.4	c.*7-58G>A		intron_variant			NP_067614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXYD2	ENST00000292079.7	c.*7-58G>A		intron_variant		1	NM_001680.5	ENSP00000292079.2
FXYD6-FXYD2	ENST00000614497.5	c.*7-58G>A		intron_variant		3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88434 AN: 151380 Hom.: 27415 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.654 AC: 274387 AN: 419728 Hom.: 91495 Cov.: 4 AF XY: 0.647 AC XY: 141812 AN XY: 219048

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.584 AC: 88471 AN: 151496 Hom.: 27428 Cov.: 31 AF XY: 0.588 AC XY: 43536 AN XY: 74012

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.578

Alfa AF: 0.586 Hom.: 11727

Bravo AF: 0.581

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs2014536; hg19: chr11-117691145;