chr11-117821619-G-A

Variant names:

• chr11-117821619-G-A
• rs4579962
• ENST00000317594.6:n.1190C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000317594.6(FXYD2):​n.1190C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 985,592 control chromosomes in the GnomAD database, including 35,491 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 0.21 (4189 hom., cov: 33)
  • Exomes 𝑓: 0.27 (31302 hom.)
• Consequence: FXYD2 ENST00000317594.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000317594.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	NM_001680.5	MANE Select	c.140-724C>T		intron	N/A	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.374-724C>T		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.312-724C>T		intron	N/A	NP_001230527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	ENST00000317594.6	TSL:1	n.1190C>T		non_coding_transcript_exon	Exon 2 of 2
	FXYD2	ENST00000292079.7	TSL:1 MANE Select	c.140-724C>T		intron	N/A	ENSP00000292079.2
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.374-724C>T		intron	N/A	ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32592 AN: 152094 Hom.: 4185 Cov.: 33

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.272 AC: 226434 AN: 833380 Hom.: 31302 Cov.: 31 AF XY: 0.272 AC XY: 104584 AN XY: 384870

African (AFR) AF: 0.0650 AC: 1026 AN: 15786

American (AMR) AF: 0.342 AC: 356 AN: 1040

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 1397 AN: 5152

East Asian (EAS) AF: 0.175 AC: 639 AN: 3642

South Asian (SAS) AF: 0.205 AC: 3374 AN: 16474

European-Finnish (FIN) AF: 0.288 AC: 80 AN: 278

Middle Eastern (MID) AF: 0.223 AC: 361 AN: 1616

European-Non Finnish (NFE) AF: 0.279 AC: 212325 AN: 762094

Other (OTH) AF: 0.252 AC: 6876 AN: 27298

GnomAD4 genome AF: 0.214 AC: 32610 AN: 152212 Hom.: 4189 Cov.: 33 AF XY: 0.212 AC XY: 15768 AN XY: 74424

African (AFR) AF: 0.0813 AC: 3377 AN: 41562

American (AMR) AF: 0.296 AC: 4529 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.162 AC: 840 AN: 5182

South Asian (SAS) AF: 0.192 AC: 926 AN: 4822

European-Finnish (FIN) AF: 0.252 AC: 2669 AN: 10604

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18692 AN: 67954

Other (OTH) AF: 0.226 AC: 478 AN: 2116

Alfa AF: 0.259 Hom.: 10889

Bravo AF: 0.213

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4579962; hg19: chr11-117692334;