1-202194068-C-T

Variant names:

• chr1-202194068-C-T
• rs1437113234
• NM_001017403.2:c.79C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001017403.2(LGR6):​c.79C>T​(p.Gln27*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,291,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: LGR6 NM_001017403.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 3 publications found

Genes affected

LGR6 (HGNC:19719): (leucine rich repeat containing G protein-coupled receptor 6) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000295211 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017403.2. 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
	LGR6	NM_001017403.2	MANE Select	c.79C>T	p.Gln27*	stop_gained	Exon 1 of 18	NP_001017403.1	Q9HBX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	ENST00000367278.8	TSL:1 MANE Select	c.79C>T	p.Gln27*	stop_gained	Exon 1 of 18	ENSP00000356247.3	Q9HBX8-3
	LGR6	ENST00000904634.1		c.79C>T	p.Gln27*	stop_gained	Exon 1 of 19	ENSP00000574693.1
	LGR6	ENST00000904651.1		c.79C>T	p.Gln27*	stop_gained	Exon 1 of 19	ENSP00000574710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 75274 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1291622 Hom.: 0 Cov.: 32 AF XY: 0.00000314 AC XY: 2 AN XY: 636894

African (AFR) AF: 0.00 AC: 0 AN: 26540

American (AMR) AF: 0.00 AC: 0 AN: 21370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21228

East Asian (EAS) AF: 0.00 AC: 0 AN: 29296

South Asian (SAS) AF: 0.00 AC: 0 AN: 66274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3722

European-Non Finnish (NFE) AF: 0.00000193 AC: 2 AN: 1036846

Other (OTH) AF: 0.00 AC: 0 AN: 53270

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.26
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.68	D
PhyloP100		1.9
Vest4		0.20
GERP RS		1.5
PromoterAI		-0.047	Neutral
Mutation Taster		=37/163	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1437113234; hg19: chr1-202163196;