chr11-117826243-C-T

Variant names:

• chr11-117826243-C-T
• rs479991
• ENST00000614497.5:c.260-3526G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204268.3(FXYD6-FXYD2):​c.260-3526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,132 control chromosomes in the GnomAD database, including 44,602 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 0.77 (44602 hom., cov: 32)
• Consequence: FXYD6-FXYD2 NM_001204268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 7 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 2

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204268.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	NM_001204268.3		c.260-3526G>A		intron	N/A	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.273-3526G>A		intron	N/A	NP_001230527.1	A0A0A6YYL5
	FXYD2	NM_021603.4		c.19+1752G>A		intron	N/A	NP_067614.1	P54710-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.260-3526G>A		intron	N/A	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.19+1752G>A		intron	N/A	ENSP00000260287.2	P54710-2
	FXYD6-FXYD2	ENST00000532984.1	TSL:3	c.273-3526G>A		intron	N/A	ENSP00000463024.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116309 AN: 152014 Hom.: 44562 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.768

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.765 AC: 116402 AN: 152132 Hom.: 44602 Cov.: 32 AF XY: 0.768 AC XY: 57081 AN XY: 74368

African (AFR) AF: 0.723 AC: 29988 AN: 41468

American (AMR) AF: 0.779 AC: 11914 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2782 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4025 AN: 5170

South Asian (SAS) AF: 0.721 AC: 3477 AN: 4820

European-Finnish (FIN) AF: 0.856 AC: 9072 AN: 10592

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52588 AN: 67998

Other (OTH) AF: 0.772 AC: 1627 AN: 2108

Alfa AF: 0.762 Hom.: 83429

Bravo AF: 0.761

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.039
DANN	Benign	0.55
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs479991; hg19: chr11-117696958;