11-117820164-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001680.5(FXYD2):c.*215G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 157,278 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (0 hom.)
• Consequence: FXYD2 NM_001680.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329

Genes affected

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]

FXYD6-FXYD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-117820164-C-T is Benign according to our data. Variant chr11-117820164-C-T is described in ClinVar as [Benign]. Clinvar id is 302513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD2	NM_001680.5	c.*215G>A		3_prime_UTR_variant	6/6	ENST00000292079.7
FXYD6-FXYD2	NM_001243598.4	c.*249G>A		3_prime_UTR_variant	10/10
FXYD6-FXYD2	NM_001204268.3	c.*215G>A		3_prime_UTR_variant	11/11
FXYD2	NM_021603.4	c.*215G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000292079.7	c.*215G>A		3_prime_UTR_variant	6/6	1	NM_001680.5
	ENST00000531850.2	n.277-297C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 774 AN: 152150 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00697

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00758 AC: 38 AN: 5010 Hom.: 0 Cov.: 0 AF XY: 0.00745 AC XY: 20 AN XY: 2686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.00573

Gnomad4 NFE exome AF: 0.00774

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.00508 AC: 774 AN: 152268 Hom.: 4 Cov.: 33 AF XY: 0.00514 AC XY: 383 AN XY: 74456

Gnomad4 AFR AF: 0.00169

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00697

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00579 Hom.: 2

Bravo AF: 0.00451

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal hypomagnesemia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.5
Dann	Benign	0.73

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: rs41304349; hg19: chr11-117690879;