ADGRV1 p.Gly5223Arg

Variant names:

• chr5-90810927-G-C
• NM_032119.4:c.15667G>C
• ADGRV1 p.Gly5223Arg

Your query was ambiguous. Multiple possible variants found:

• chr5-90810927-G-C
• chr5-90810927-G-A
• chr5-90810927-GGG-CGT
• chr5-90810927-GGG-CGC
• chr5-90810927-GGG-CGA
• chr5-90810927-GGG-AGA

Variant summary

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

The NM_032119.4(ADGRV1):​c.15667G>C​(p.Gly5223Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G5223G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

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_032119.4. 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
	ADGRV1	NM_032119.4	MANE Select	c.15667G>C	p.Gly5223Arg	missense	Exon 74 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.15683G>C		non_coding_transcript_exon	Exon 74 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.15667G>C	p.Gly5223Arg	missense	Exon 74 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.2934G>C		non_coding_transcript_exon	Exon 10 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.4621G>C	p.Gly1541Arg	missense	Exon 22 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.89	T
PhyloP100		6.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.33
gMVP		0.77
Mutation Taster		=50/50

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-90106744;