rs2797221

Positions:

• chr1-215739300-T-C
• chr1-215739300-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_206933.4(USH2A):​c.11711+2075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,202 control chromosomes in the GnomAD database, including 59,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59950 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.11711+2075A>G		intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.11711+2075A>G		intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000674083.1	c.11711+2075A>G		intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133550 AN: 152086 Hom.: 59921 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.878 AC: 133629 AN: 152202 Hom.: 59950 Cov.: 32 AF XY: 0.876 AC XY: 65218 AN XY: 74426

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.907

Alfa AF: 0.923 Hom.: 9588

Bravo AF: 0.857

Asia WGS AF: 0.761 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.86

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: rs2797221; hg19: chr1-215912642;