rs4579962

chr11-117821619-G-Achr11-117821619-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001680.5(FXYD2):c.140-724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 985,592 control chromosomes in the GnomAD database, including 35,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4189 hom., cov: 33)
  • Exomes 𝑓: 0.27 (31302 hom.)
• Consequence: FXYD2 NM_001680.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD2	NM_001680.5	c.140-724C>T		intron_variant		ENST00000292079.7
FXYD6-FXYD2	NM_001243598.4	c.312-724C>T		intron_variant
FXYD6-FXYD2	NM_001204268.3	c.374-724C>T		intron_variant
FXYD2	NM_021603.4	c.134-724C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000292079.7	c.140-724C>T		intron_variant		1	NM_001680.5
	ENST00000531850.2	n.538-354G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32592 AN: 152094 Hom.: 4185 Cov.: 33

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.272 AC: 226434 AN: 833380 Hom.: 31302 Cov.: 31 AF XY: 0.272 AC XY: 104584 AN XY: 384870

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.214 AC: 32610 AN: 152212 Hom.: 4189 Cov.: 33 AF XY: 0.212 AC XY: 15768 AN XY: 74424

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.226

Alfa AF: 0.266 Hom.: 7561

Bravo AF: 0.213

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.20
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4579962; hg19: chr11-117692334;