chr11-117820548-C-A

Position:

• chr11-117820548-C-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD2	NM_001680.5	c.*6+118G>T		intron_variant		ENST00000292079.7
FXYD6-FXYD2	NM_001243598.4	c.*40+118G>T		intron_variant
FXYD6-FXYD2	NM_001204268.3	c.*6+118G>T		intron_variant
FXYD2	NM_021603.4	c.*6+118G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD2	ENST00000292079.7	c.*6+118G>T		intron_variant		1	NM_001680.5
	ENST00000531850.2	n.364C>A		non_coding_transcript_exon_variant	2/3	5

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

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00672

Gnomad4 FIN exome AF: 0.000380

Gnomad4 NFE exome AF: 0.00437

Gnomad4 OTH exome AF: 0.00972

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

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00504

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0134 Hom.: 2

Bravo AF: 0.0170

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs114805473; hg19: chr11-117691263;