rs1215540106

Variant names:

• chr1-216198562-TAGT-C
• rs1215540106
• NM_206933.4:c.3831_3834delACTAinsG

Your query was ambiguous. Multiple possible variants found:

• chr1-216198561-ATAGT-AC
• chr1-216198561-ATAGT-AT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_206933.4(USH2A):​c.3831_3834delACTAinsG​(p.Leu1278del) variant causes a conservative inframe deletion, synonymous change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E1277E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USH2A NM_206933.4 conservative_inframe_deletion, synonymous
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.93
• Publications: 0 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-AS1 (HGNC:40606): (USH2A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_206933.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 1-216198562-TAGT-C is Pathogenic according to our data. Variant chr1-216198562-TAGT-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 438019.Status of the report is no_assertion_criteria_provided, 0 stars.

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.3831_3834delACTAinsG	p.Leu1278del	conservative_inframe_deletion synonymous	Exon 18 of 72	NP_996816.3	O75445-1
	USH2A	NM_007123.6		c.3831_3834delACTAinsG	p.Leu1278del	conservative_inframe_deletion synonymous	Exon 18 of 21	NP_009054.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.3831_3834delACTAinsG	p.Leu1278del	conservative_inframe_deletion synonymous	Exon 18 of 72	ENSP00000305941.3	O75445-1
	USH2A	ENST00000366942.3	TSL:1	c.3831_3834delACTAinsG	p.Leu1278del	conservative_inframe_deletion synonymous	Exon 18 of 21	ENSP00000355909.3	O75445-2
	USH2A	ENST00000674083.1		c.3831_3834delACTAinsG	p.Leu1278del	conservative_inframe_deletion synonymous	Exon 18 of 73	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Usher syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9
Mutation Taster		=15/85	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1215540106; hg19: chr1-216371904;