11-117820430-C-T

Variant names:

• chr11-117820430-C-T
• rs2014536
• NM_001680.5:c.*7-58G>A

Variant summary

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

The NM_001680.5(FXYD2):​c.*7-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 571,224 control chromosomes in the GnomAD database, including 118,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27428 hom., cov: 31)
  • Exomes 𝑓: 0.65 (91495 hom.)
• Consequence: FXYD2 NM_001680.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.02
• Publications: 3 publications found

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: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]

ENSG00000254844 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-117820430-C-T is Benign according to our data. Variant chr11-117820430-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001680.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	NM_001680.5	MANE Select	c.*7-58G>A		intron	N/A	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.*7-58G>A		intron	N/A	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.*41-58G>A		intron	N/A	NP_001230527.1	A0A0A6YYL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	ENST00000292079.7	TSL:1 MANE Select	c.*7-58G>A		intron	N/A	ENSP00000292079.2	P54710-1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.*7-58G>A		intron	N/A	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.*7-58G>A		intron	N/A	ENSP00000260287.2	P54710-2

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88434 AN: 151380 Hom.: 27415 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.654 AC: 274387 AN: 419728 Hom.: 91495 Cov.: 4 AF XY: 0.647 AC XY: 141812 AN XY: 219048

African (AFR) AF: 0.365 AC: 4303 AN: 11776

American (AMR) AF: 0.752 AC: 12772 AN: 16982

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 8058 AN: 12932

East Asian (EAS) AF: 0.685 AC: 19896 AN: 29064

South Asian (SAS) AF: 0.492 AC: 17569 AN: 35696

European-Finnish (FIN) AF: 0.750 AC: 20788 AN: 27732

Middle Eastern (MID) AF: 0.558 AC: 1128 AN: 2022

European-Non Finnish (NFE) AF: 0.673 AC: 174165 AN: 258922

Other (OTH) AF: 0.638 AC: 15708 AN: 24602

GnomAD4 genome AF: 0.584 AC: 88471 AN: 151496 Hom.: 27428 Cov.: 31 AF XY: 0.588 AC XY: 43536 AN XY: 74012

African (AFR) AF: 0.361 AC: 14925 AN: 41350

American (AMR) AF: 0.695 AC: 10585 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2153 AN: 3462

East Asian (EAS) AF: 0.673 AC: 3446 AN: 5122

South Asian (SAS) AF: 0.482 AC: 2323 AN: 4816

European-Finnish (FIN) AF: 0.740 AC: 7759 AN: 10490

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45393 AN: 67728

Other (OTH) AF: 0.578 AC: 1212 AN: 2098

Alfa AF: 0.596 Hom.: 15058

Bravo AF: 0.581

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.47
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2014536; hg19: chr11-117691145;