11-117828871-T-G

Variant names:

• chr11-117828871-T-G
• rs10892181
• ENST00000614497.5:c.260-6154A>C

Variant summary

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

The ENST00000614497.5(FXYD6-FXYD2):​c.260-6154A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,012 control chromosomes in the GnomAD database, including 9,746 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 0.35 (9746 hom., cov: 34)
• Consequence: FXYD6-FXYD2 ENST00000614497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 4 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000614497.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	NM_001204268.3		c.260-6154A>C		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.273-6154A>C		intron	N/A	NP_001230527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.260-6154A>C		intron	N/A	ENSP00000482442.1
	FXYD6-FXYD2	ENST00000532984.1	TSL:3	c.273-6154A>C		intron	N/A	ENSP00000463024.1
	FXYD2	ENST00000528014.5	TSL:3	c.-341A>C		upstream_gene	N/A	ENSP00000432430.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52845 AN: 151892 Hom.: 9744 Cov.: 34

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.348 AC: 52882 AN: 152012 Hom.: 9746 Cov.: 34 AF XY: 0.355 AC XY: 26382 AN XY: 74316

African (AFR) AF: 0.251 AC: 10397 AN: 41476

American (AMR) AF: 0.442 AC: 6747 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2534 AN: 5160

South Asian (SAS) AF: 0.325 AC: 1565 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4986 AN: 10568

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24537 AN: 67936

Other (OTH) AF: 0.339 AC: 715 AN: 2110

Alfa AF: 0.289 Hom.: 1477

Bravo AF: 0.344

Asia WGS AF: 0.397 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		1.0
PromoterAI		0.12	Neutral
Mutation Taster		=99/1	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: rs10892181; hg19: chr11-117699586;