1-216258898-A-G

Variant names:

• chr1-216258898-A-G
• rs10864235
• NM_206933.4:c.1972-7800T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206933.4(USH2A):​c.1972-7800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,872 control chromosomes in the GnomAD database, including 26,954 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 0.58 (26954 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 3 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 2

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

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.1972-7800T>C		intron	N/A	NP_996816.3
	USH2A	NM_007123.6		c.1972-7800T>C		intron	N/A	NP_009054.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.1972-7800T>C		intron	N/A	ENSP00000305941.3
	USH2A	ENST00000366942.3	TSL:1	c.1972-7800T>C		intron	N/A	ENSP00000355909.3
	USH2A	ENST00000674083.1		c.1972-7800T>C		intron	N/A	ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87520 AN: 151754 Hom.: 26941 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.577 AC: 87556 AN: 151872 Hom.: 26954 Cov.: 32 AF XY: 0.585 AC XY: 43425 AN XY: 74262

African (AFR) AF: 0.336 AC: 13903 AN: 41434

American (AMR) AF: 0.664 AC: 10112 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2147 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3689 AN: 5142

South Asian (SAS) AF: 0.686 AC: 3311 AN: 4824

European-Finnish (FIN) AF: 0.768 AC: 8122 AN: 10582

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44159 AN: 67870

Other (OTH) AF: 0.600 AC: 1264 AN: 2106

Alfa AF: 0.607 Hom.: 4844

Bravo AF: 0.560

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs10864235; hg19: chr1-216432240;