1-215817098-G-C

Variant names:

• chr1-215817098-G-C
• rs772100045
• NM_206933.4:c.9469C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206933.4(USH2A):​c.9469C>G​(p.Gln3157Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: USH2A NM_206933.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 9 publications found

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

USH2A Gene-Disease associations (from GenCC):

• Usher syndrome type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 2

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• retinitis pigmentosa 39

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10631046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206933.4. 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
	USH2A	NM_206933.4	MANE Select	c.9469C>G	p.Gln3157Glu	missense	Exon 48 of 72	NP_996816.3	O75445-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.9469C>G	p.Gln3157Glu	missense	Exon 48 of 72	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.9469C>G	p.Gln3157Glu	missense	Exon 48 of 73	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250496 AF XY: 0.00000739

Gnomad AFR exome AF: 0.0000616

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: 6.85e-7 AC: 1 AN: 1460800 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726704

African (AFR) AF: 0.0000299 AC: 1 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111170

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.4
DANN	Benign	0.53
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.032
Sift	Benign	0.40	T
Sift4G	Benign	0.42	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.42		Gain of loop (P = 0.1069)
MVP		0.65
MPC		0.034
ClinPred		0.049	T
GERP RS		3.4
Varity_R		0.063
gMVP		0.24
Mutation Taster		=86/14	polymorphism

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: rs772100045; hg19: chr1-215990440;