rs11216567

Positions:

• chr11-117827768-A-G

Variant summary

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

The NM_001243598.4(FXYD6-FXYD2):​c.273-5051T>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 NM_001243598.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00900

Genes affected

FXYD6-FXYD2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
FXYD6-FXYD2	NM_001243598.4	c.273-5051T>C		intron_variant
FXYD6-FXYD2	NM_001204268.3	c.260-5051T>C		intron_variant
FXYD2	NM_021603.4	c.19+227T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000260287.2	c.19+227T>C		intron_variant		1		P1
FXYD2	ENST00000528014.5	c.19+227T>C		intron_variant		3		P1
FXYD2	ENST00000532119.5	c.19+227T>C		intron_variant		3		P1

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0907 Hom.: 1478

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.50

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: rs11216567; hg19: chr11-117698483;