rs2252865

Variant names:

• chr1-8362616-T-A
• rs2252865
• NM_001042681.2:c.1902+67A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-8362616-T-A
• chr1-8362616-T-C
• chr1-8362616-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042681.2(RERE):​c.1902+67A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RERE NM_001042681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 0 publications found

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]

RERE Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder with or without congenital anomalies

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042681.2. 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
	RERE	NM_001042681.2	MANE Select	c.1902+67A>T		intron	N/A	NP_001036146.1	Q9P2R6-1
	RERE	NM_012102.4		c.1902+67A>T		intron	N/A	NP_036234.3
	RERE	NM_001042682.2		c.240+67A>T		intron	N/A	NP_001036147.1	Q9P2R6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERE	ENST00000400908.7	TSL:1 MANE Select	c.1902+67A>T		intron	N/A	ENSP00000383700.2	Q9P2R6-1
	RERE	ENST00000337907.7	TSL:1	c.1902+67A>T		intron	N/A	ENSP00000338629.3	Q9P2R6-1
	RERE	ENST00000476556.5	TSL:1	c.240+67A>T		intron	N/A	ENSP00000422246.1	Q9P2R6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1445336 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 719590

African (AFR) AF: 0.00 AC: 0 AN: 33144

American (AMR) AF: 0.00 AC: 0 AN: 44122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098624

Other (OTH) AF: 0.00 AC: 0 AN: 59868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.59
PhyloP100		-0.24
PromoterAI		0.019	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2252865; hg19: chr1-8422676;