chr1-8358216-TGGTGGAGGTGGA-T

Variant names:

• chr1-8358216-TGGTGGAGGTGGA-T
• NM_001042681.2:c.4307_4318delTCCACCTCCACC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 7P and 1B. PM1 PM2 PP3 PP5_Moderate BP3

The NM_001042681.2(RERE):​c.4307_4318delTCCACCTCCACC​(p.Leu1436_His1439del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RERE NM_001042681.2 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.97

Genes affected

RERE (HGNC:9965): (arginine-glutamic acid dipeptide repeats) This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 2 uncertain in NM_001042681.2
• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-8358216-TGGTGGAGGTGGA-T is Pathogenic according to our data. Variant chr1-8358216-TGGTGGAGGTGGA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2442107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP3: Nonframeshift variant in repetitive region in NM_001042681.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERE	NM_001042681.2	c.4307_4318delTCCACCTCCACC	p.Leu1436_His1439del	disruptive_inframe_deletion	Exon 20 of 23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.4307_4318delTCCACCTCCACC	p.Leu1436_His1439del	disruptive_inframe_deletion	Exon 21 of 24		NP_036234.3
RERE	NM_001042682.2	c.2645_2656delTCCACCTCCACC	p.Leu882_His885del	disruptive_inframe_deletion	Exon 10 of 13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.4307_4318delTCCACCTCCACC	p.Leu1436_His1439del	disruptive_inframe_deletion	Exon 20 of 23	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart Pathogenic:1

Mar 06, 2022

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-8418276;