rs114805473

Variant names:

• chr11-117820548-C-A
• rs114805473
• NM_001680.5:c.*6+118G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001680.5(FXYD2):​c.*6+118G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,300,516 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (66 hom.)
• Consequence: FXYD2 NM_001680.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.317
• 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 -16 ACMG points.

• BP6: Variant 11-117820548-C-A is Benign according to our data. Variant chr11-117820548-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1317355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2234/152320) while in subpopulation AFR AF = 0.037 (1536/41566). AF 95% confidence interval is 0.0354. There are 32 homozygotes in GnomAd4. There are 1072 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2234 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.*6+118G>T		intron	N/A	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.*6+118G>T		intron	N/A	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.*40+118G>T		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.*6+118G>T		intron	N/A	ENSP00000292079.2	P54710-1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.*6+118G>T		intron	N/A	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.*6+118G>T		intron	N/A	ENSP00000260287.2	P54710-2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2230 AN: 152202 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.00567 AC: 6508 AN: 1148196 Hom.: 66 Cov.: 15 AF XY: 0.00577 AC XY: 3336 AN XY: 577774

African (AFR) AF: 0.0393 AC: 1083 AN: 27590

American (AMR) AF: 0.00776 AC: 315 AN: 40596

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 237 AN: 21554

East Asian (EAS) AF: 0.00 AC: 0 AN: 37562

South Asian (SAS) AF: 0.00672 AC: 489 AN: 72734

European-Finnish (FIN) AF: 0.000380 AC: 18 AN: 47370

Middle Eastern (MID) AF: 0.0366 AC: 184 AN: 5030

European-Non Finnish (NFE) AF: 0.00437 AC: 3698 AN: 845982

Other (OTH) AF: 0.00972 AC: 484 AN: 49778

GnomAD4 genome AF: 0.0147 AC: 2234 AN: 152320 Hom.: 32 Cov.: 32 AF XY: 0.0144 AC XY: 1072 AN XY: 74472

African (AFR) AF: 0.0370 AC: 1536 AN: 41566

American (AMR) AF: 0.0156 AC: 238 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00504 AC: 343 AN: 68030

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0143 Hom.: 3

Bravo AF: 0.0170

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.87
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs114805473; hg19: chr11-117691263;