rs869789

Variant names:

• chr11-117820671-G-A
• rs869789
• NM_001680.5:c.*1C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-117820671-G-A
• chr11-117820671-G-C
• chr11-117820671-G-T

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.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,726 control chromosomes in the GnomAD database, including 15,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1373 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14620 hom.)
• Consequence: FXYD2 NM_001680.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.527
• Publications: 15 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=-0.87).
• BP6: Variant 11-117820671-G-A is Benign according to our data. Variant chr11-117820671-G-A is described in ClinVar as Benign. ClinVar VariationId is 302521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD2	NM_001680.5	c.*1C>T		3_prime_UTR_variant	Exon 5 of 6	ENST00000292079.7	NP_001671.2
FXYD6-FXYD2	NM_001204268.3	c.*1C>T		3_prime_UTR_variant	Exon 10 of 11		NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.*35C>T		3_prime_UTR_variant	Exon 9 of 10		NP_001230527.1
FXYD2	NM_021603.4	c.*1C>T		3_prime_UTR_variant	Exon 5 of 6		NP_067614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD2	ENST00000292079.7	c.*1C>T		3_prime_UTR_variant	Exon 5 of 6	1	NM_001680.5	ENSP00000292079.2
FXYD6-FXYD2	ENST00000614497.5	c.*1C>T		3_prime_UTR_variant	Exon 10 of 11	3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19627 AN: 152052 Hom.: 1370 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.139 AC: 34821 AN: 250982 AF XY: 0.131

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.137 AC: 200385 AN: 1461556 Hom.: 14620 Cov.: 33 AF XY: 0.134 AC XY: 97090 AN XY: 727110

African (AFR) AF: 0.0930 AC: 3112 AN: 33466

American (AMR) AF: 0.225 AC: 10047 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3022 AN: 26132

East Asian (EAS) AF: 0.216 AC: 8561 AN: 39698

South Asian (SAS) AF: 0.0445 AC: 3840 AN: 86252

European-Finnish (FIN) AF: 0.134 AC: 7169 AN: 53334

Middle Eastern (MID) AF: 0.144 AC: 832 AN: 5764

European-Non Finnish (NFE) AF: 0.140 AC: 155379 AN: 1111822

Other (OTH) AF: 0.139 AC: 8423 AN: 60382

GnomAD4 genome AF: 0.129 AC: 19650 AN: 152170 Hom.: 1373 Cov.: 32 AF XY: 0.129 AC XY: 9565 AN XY: 74374

African (AFR) AF: 0.0931 AC: 3864 AN: 41522

American (AMR) AF: 0.178 AC: 2716 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.191 AC: 987 AN: 5168

South Asian (SAS) AF: 0.0447 AC: 216 AN: 4830

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9614 AN: 67982

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.134 Hom.: 3050

Bravo AF: 0.136

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 26, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Renal hypomagnesemia 2 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs869789; hg19: chr11-117691386; COSMIC: COSV52643034; COSMIC: COSV52643034;