1-215741541-GAA-GAAAA

Position:

• chr1-215741541-GAA-GAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206933.4(USH2A):​c.11549-5_11549-4insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,087,750 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH2A NM_206933.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.11549-5_11549-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.11549-5_11549-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000674083.1	c.11549-5_11549-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 138820 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000271 AC: 32 AN: 118084 Hom.: 0 AF XY: 0.000253 AC XY: 16 AN XY: 63212

Gnomad AFR exome AF: 0.000340

Gnomad AMR exome AF: 0.000445

Gnomad ASJ exome AF: 0.000289

Gnomad EAS exome AF: 0.000228

Gnomad SAS exome AF: 0.000346

Gnomad FIN exome AF: 0.000296

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000388

GnomAD4 exome AF: 0.0000322 AC: 35 AN: 1087750 Hom.: 0 Cov.: 33 AF XY: 0.0000351 AC XY: 19 AN XY: 540740

Gnomad4 AFR exome AF: 0.000166

Gnomad4 AMR exome AF: 0.000404

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000342

Gnomad4 SAS exome AF: 0.0000324

Gnomad4 FIN exome AF: 0.0000777

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000451

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 138820 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 66874

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34565443; hg19: chr1-215914883;