rs572910896

Variant names:

• chr5-90685795-G-A
• rs572910896
• NM_032119.4:c.6290G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90685795-G-A
• chr5-90685795-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_032119.4(ADGRV1):​c.6290G>A​(p.Arg2097His) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,455,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2097L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 6.31
• Publications: 5 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: Orphanet, ClinGen
• 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: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 5-90685795-G-A is Benign according to our data. Variant chr5-90685795-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 502636.

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.6290G>A	p.Arg2097His	missense	Exon 29 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.6389G>A		non_coding_transcript_exon	Exon 29 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6290G>A	p.Arg2097His	missense	Exon 29 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.3581G>A	p.Arg1194His	missense	Exon 19 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.1749G>A		non_coding_transcript_exon	Exon 9 of 23

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245446 AF XY: 0.00

Gnomad AFR exome AF: 0.0000647

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: 0.00000412 AC: 6 AN: 1455730 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724308

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50438

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109882

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.76	T
PhyloP100		6.3
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.42		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.74
MPC		0.34
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.52
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs572910896; hg19: chr5-89981612; COSMIC: COSV67996966;