dbSNP rs777843062: RELN:p.Cys2732Phe (chr7-103510930-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005045.4(RELN):c.8195G>T(p.Cys2732Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RELN
NM_005045.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.57

Publications

0 publications found

Variant links:

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

RELN links:

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

SLC26A5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RELN	NM_005045.4	MANE Select	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	NP_005036.2
RELN	NM_173054.3		c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 64	NP_774959.1	P78509-2
SLC26A5-AS1	NR_110141.1		n.1487-1839C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RELN	ENST00000428762.6	TSL:5 MANE Select	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	ENSP00000392423.1	P78509-1
SLC26A5-AS1	ENST00000422488.1	TSL:1	n.1487-1839C>A		intron	N/A
RELN	ENST00000424685.3	TSL:5	c.8195G>T	p.Cys2732Phe	missense	Exon 51 of 65	ENSP00000388446.3	J3KQ66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726580

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110666

Other (OTH)

AF:

0.00

AC:

AN:

60348

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial temporal lobe epilepsy 7 (1)

Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.59

PhyloP100

6.6

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.45

Sift

Benign

0.41

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.95

MutPred

0.52

Loss of catalytic residue at M2730 (P = 0.0099)

MVP

0.46

MPC

1.2

ClinPred

0.97

GERP RS

5.7

Varity_R

0.49

gMVP

0.71

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over