NM_001680.5:c.183C>T

Variant names:

• chr11-117820690-G-A
• rs201669990
• NM_001680.5:c.183C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001680.5(FXYD2):​c.183C>T​(p.Ile61Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: FXYD2 NM_001680.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0960
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-117820690-G-A is Benign according to our data. Variant chr11-117820690-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 302523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.
• BS2: High AC in GnomAd4 at 21 AD gene.

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.183C>T	p.Ile61Ile	synonymous	Exon 5 of 6	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.417C>T	p.Ile139Ile	synonymous	Exon 10 of 11	NP_001191197.1	A0A087WZ82
	FXYD2	NM_021603.4		c.177C>T	p.Ile59Ile	synonymous	Exon 5 of 6	NP_067614.1	P54710-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	ENST00000292079.7	TSL:1 MANE Select	c.183C>T	p.Ile61Ile	synonymous	Exon 5 of 6	ENSP00000292079.2	P54710-1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.417C>T	p.Ile139Ile	synonymous	Exon 10 of 11	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.177C>T	p.Ile59Ile	synonymous	Exon 5 of 6	ENSP00000260287.2	P54710-2

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250986 AF XY: 0.0000958

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000817

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461772 Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 32 AN XY: 727194

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111988

Other (OTH) AF: 0.000298 AC: 18 AN: 60388

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74402

African (AFR) AF: 0.000265 AC: 11 AN: 41486

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000170

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Renal hypomagnesemia 2 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		-0.096

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: rs201669990; hg19: chr11-117691405;