ENST00000614497.5:c.260-5051T>C

Variant names:

• chr11-117827768-A-G
• rs11216567
• ENST00000614497.5:c.260-5051T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000614497.5(FXYD6-FXYD2):​c.260-5051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,216 control chromosomes in the GnomAD database, including 1,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.11 (1085 hom., cov: 33)
• Consequence: FXYD6-FXYD2 ENST00000614497.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00900
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-117827768-A-G is Benign according to our data. Variant chr11-117827768-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD6-FXYD2	NM_001204268.3	c.260-5051T>C		intron_variant	Intron 6 of 10		NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.273-5051T>C		intron_variant	Intron 6 of 9		NP_001230527.1
FXYD2	NM_021603.4	c.19+227T>C		intron_variant	Intron 1 of 5		NP_067614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD6-FXYD2	ENST00000614497.5	c.260-5051T>C		intron_variant	Intron 6 of 10	3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17075 AN: 152096 Hom.: 1084 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.112 AC: 17088 AN: 152216 Hom.: 1085 Cov.: 33 AF XY: 0.114 AC XY: 8485 AN XY: 74418

African (AFR) AF: 0.159 AC: 6589 AN: 41506

American (AMR) AF: 0.110 AC: 1676 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1064 AN: 5184

South Asian (SAS) AF: 0.123 AC: 591 AN: 4820

European-Finnish (FIN) AF: 0.0654 AC: 694 AN: 10616

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5918 AN: 68010

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.0939 Hom.: 3338

Bravo AF: 0.114

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.50
PhyloP100		-0.0090
PromoterAI		-0.023	Neutral
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: rs11216567; hg19: chr11-117698483;