rs147985313

Variant names:

• chr1-8359808-GCTCCTTCTCCTT-G
• rs147985313
• NM_001042681.2:c.3562_3573delAAGGAGAAGGAG

Your query was ambiguous. Multiple possible variants found:

• chr1-8359808-GCTCCTTCTCCTT-G
• chr1-8359808-GCTCCTTCTCCTT-GCTCCTT
• chr1-8359808-GCTCCTTCTCCTT-GCTCCTTCTCCTTCTCCTT
• chr1-8359808-GCTCCTTCTCCTT-GCTCCTTCTCCTTCTCCTTCTCCTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP3 BP3 BS2

The NM_001042681.2(RERE):​c.3562_3573delAAGGAGAAGGAG​(p.Lys1188_Glu1191del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,604,454 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RERE NM_001042681.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• Publications: 2 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 -4 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP3: Nonframeshift variant in repetitive region in NM_001042681.2
• BS2: High AC in GnomAdExome4 at 41 AD gene.

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.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 19 of 23	NP_001036146.1	Q9P2R6-1
	RERE	NM_012102.4		c.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 20 of 24	NP_036234.3
	RERE	NM_001042682.2		c.1900_1911delAAGGAGAAGGAG	p.Lys634_Glu637del	conservative_inframe_deletion	Exon 9 of 13	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.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 19 of 23	ENSP00000383700.2	Q9P2R6-1
	RERE	ENST00000337907.7	TSL:1	c.3562_3573delAAGGAGAAGGAG	p.Lys1188_Glu1191del	conservative_inframe_deletion	Exon 20 of 24	ENSP00000338629.3	Q9P2R6-1
	RERE	ENST00000476556.5	TSL:1	c.1900_1911delAAGGAGAAGGAG	p.Lys634_Glu637del	conservative_inframe_deletion	Exon 9 of 13	ENSP00000422246.1	Q9P2R6-2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151650 Hom.: 0 Cov.: 30

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1452804 Hom.: 0 AF XY: 0.0000332 AC XY: 24 AN XY: 723170

African (AFR) AF: 0.0000598 AC: 2 AN: 33448

American (AMR) AF: 0.0000224 AC: 1 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111198

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151650 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74044

African (AFR) AF: 0.00 AC: 0 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=65/135	disease causing

Splicing

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

Other links and lift over

dbSNP: rs147985313; hg19: chr1-8419868;