rs678776

Positions:

• chr11-117826029-G-A
• chr11-117826029-G-T

Variant summary

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

The NM_001243598.4(FXYD6-FXYD2):​c.273-3312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,116 control chromosomes in the GnomAD database, including 4,749 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 0.24 (4749 hom., cov: 32)
• Consequence: FXYD6-FXYD2 NM_001243598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD6-FXYD2	NM_001243598.4	c.273-3312C>T		intron_variant
FXYD6-FXYD2	NM_001204268.3	c.260-3312C>T		intron_variant
FXYD2	NM_021603.4	c.19+1966C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000260287.2	c.19+1966C>T		intron_variant		1		P1
FXYD2	ENST00000528014.5	c.19+1966C>T		intron_variant		3		P1
FXYD2	ENST00000532119.5	c.19+1966C>T		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35943 AN: 151996 Hom.: 4745 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.236 AC: 35954 AN: 152116 Hom.: 4749 Cov.: 32 AF XY: 0.235 AC XY: 17505 AN XY: 74384

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.264

Alfa AF: 0.280 Hom.: 3501

Bravo AF: 0.228

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.43

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: rs678776; hg19: chr11-117696744;