chr11-117820637-C-T

Variant names:

• chr11-117820637-C-T
• rs118032332
• NM_001680.5:c.*6+29G>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.*6+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,456 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: FXYD2 NM_001680.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.158
• Publications: 1 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=-0.88).
• BP6: Variant 11-117820637-C-T is Benign according to our data. Variant chr11-117820637-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0519 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.*6+29G>A		intron	N/A	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.*6+29G>A		intron	N/A	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.*40+29G>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.*6+29G>A		intron	N/A	ENSP00000292079.2	P54710-1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.*6+29G>A		intron	N/A	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.*6+29G>A		intron	N/A	ENSP00000260287.2	P54710-2

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 341 AN: 152154 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00447 AC: 1120 AN: 250342 AF XY: 0.00407

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0578

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00156 AC: 2273 AN: 1461184 Hom.: 52 Cov.: 31 AF XY: 0.00151 AC XY: 1096 AN XY: 726940

African (AFR) AF: 0.000149 AC: 5 AN: 33470

American (AMR) AF: 0.000201 AC: 9 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.0472 AC: 1872 AN: 39692

South Asian (SAS) AF: 0.00136 AC: 117 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111568

Other (OTH) AF: 0.00383 AC: 231 AN: 60364

GnomAD4 genome AF: 0.00223 AC: 339 AN: 152272 Hom.: 11 Cov.: 32 AF XY: 0.00239 AC XY: 178 AN XY: 74458

African (AFR) AF: 0.000120 AC: 5 AN: 41552

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0573 AC: 297 AN: 5184

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000648 Hom.: 1

Bravo AF: 0.00244

Asia WGS AF: 0.0260 AC: 90 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	-0.88
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.16
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism

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: rs118032332; hg19: chr11-117691352;