rs55713064

Variant names:

• chr1-215878724-G-T
• rs55713064
• NM_206933.4:c.8558+40C>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_206933.4(USH2A):​c.8558+40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 1,592,782 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (8 hom., cov: 32)
  • Exomes 𝑓: 0.010 (96 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00500
• Publications: 1 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, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-215878724-G-T is Benign according to our data. Variant chr1-215878724-G-T is described in ClinVar as Benign. ClinVar VariationId is 403599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

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.8558+40C>A		intron	N/A	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.8558+40C>A		intron	N/A	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.8558+40C>A		intron	N/A	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1163 AN: 152104 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00859 AC: 2036 AN: 236936 AF XY: 0.00875

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00777

Gnomad ASJ exome AF: 0.0188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00666

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0101 AC: 14617 AN: 1440560 Hom.: 96 Cov.: 28 AF XY: 0.0103 AC XY: 7363 AN XY: 716712

African (AFR) AF: 0.00245 AC: 81 AN: 33046

American (AMR) AF: 0.00815 AC: 357 AN: 43822

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 563 AN: 25856

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39462

South Asian (SAS) AF: 0.00441 AC: 373 AN: 84664

European-Finnish (FIN) AF: 0.00633 AC: 336 AN: 53056

Middle Eastern (MID) AF: 0.0135 AC: 74 AN: 5468

European-Non Finnish (NFE) AF: 0.0112 AC: 12261 AN: 1095474

Other (OTH) AF: 0.00956 AC: 571 AN: 59712

GnomAD4 genome AF: 0.00764 AC: 1163 AN: 152222 Hom.: 8 Cov.: 32 AF XY: 0.00750 AC XY: 558 AN XY: 74422

African (AFR) AF: 0.00253 AC: 105 AN: 41552

American (AMR) AF: 0.00883 AC: 135 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4822

European-Finnish (FIN) AF: 0.00472 AC: 50 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 744 AN: 68008

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.0101 Hom.: 2

Bravo AF: 0.00800

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa 39 (1)
-	-	1	Usher syndrome type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.57
PhyloP100		0.0050
Mutation Taster		=100/0	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: rs55713064; hg19: chr1-216052066;