11-117820678-C-T

Position:

• chr11-117820678-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001680.5(FXYD2):​c.195G>A​(p.Glu65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,614,038 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (90 hom.)
• Consequence: FXYD2 NM_001680.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.50

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-117820678-C-T is Benign according to our data. Variant chr11-117820678-C-T is described in ClinVar as [Benign]. Clinvar id is 302522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00418 (636/152276) while in subpopulation SAS AF= 0.0195 (94/4826). AF 95% confidence interval is 0.0163. There are 7 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 636 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD2	NM_001680.5	c.195G>A	p.Glu65=	synonymous_variant	5/6	ENST00000292079.7
FXYD6-FXYD2	NM_001243598.4	c.*28G>A		3_prime_UTR_variant	9/10
FXYD6-FXYD2	NM_001204268.3	c.429G>A	p.Glu143=	synonymous_variant	10/11
FXYD2	NM_021603.4	c.189G>A	p.Glu63=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000292079.7	c.195G>A	p.Glu65=	synonymous_variant	5/6	1	NM_001680.5
	ENST00000531850.2	n.494C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 637 AN: 152158 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00598

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00682 AC: 1712 AN: 251096 Hom.: 26 AF XY: 0.00779 AC XY: 1058 AN XY: 135748

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0228

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00680

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00650 AC: 9496 AN: 1461762 Hom.: 90 Cov.: 33 AF XY: 0.00695 AC XY: 5054 AN XY: 727186

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0226

Gnomad4 FIN exome AF: 0.00141

Gnomad4 NFE exome AF: 0.00595

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.00418 AC: 636 AN: 152276 Hom.: 7 Cov.: 31 AF XY: 0.00418 AC XY: 311 AN XY: 74464

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00600

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00536 Hom.: 2

Bravo AF: 0.00376

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00581

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -

Renal hypomagnesemia 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.74

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: rs144519777; hg19: chr11-117691393;