rs144519777

Variant names:

• chr11-117820678-C-A
• rs144519777
• NM_001680.5:c.195G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-117820678-C-A
• chr11-117820678-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001680.5(FXYD2):​c.195G>T​(p.Glu65Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E65E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FXYD2 NM_001680.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06264952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD2	NM_001680.5	c.195G>T	p.Glu65Asp	missense_variant	Exon 5 of 6	ENST00000292079.7	NP_001671.2
FXYD6-FXYD2	NM_001204268.3	c.429G>T	p.Glu143Asp	missense_variant	Exon 10 of 11		NP_001191197.1
FXYD2	NM_021603.4	c.189G>T	p.Glu63Asp	missense_variant	Exon 5 of 6		NP_067614.1
FXYD6-FXYD2	NM_001243598.4	c.*28G>T		3_prime_UTR_variant	Exon 9 of 10		NP_001230527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD2	ENST00000292079.7	c.195G>T	p.Glu65Asp	missense_variant	Exon 5 of 6	1	NM_001680.5	ENSP00000292079.2
FXYD6-FXYD2	ENST00000614497.5	c.429G>T	p.Glu143Asp	missense_variant	Exon 10 of 11	3		ENSP00000482442.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.97
DANN	Benign	0.93
DEOGEN2	Benign	0.14	.;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.19	.;.;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.063	T;T;T;T;T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-1.6	N;N;N;N;.
REVEL	Benign	0.074
Sift	Benign	0.11	T;T;T;T;.
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.0030	B;B;B;B;.
Vest4		0.21
MutPred		0.21		.;.;Gain of MoRF binding (P = 0.1775);.;.;
MVP		0.23
MPC		0.12
ClinPred		0.047	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.057
gMVP		0.087

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs144519777; hg19: chr11-117691393;