Genetic Variant NM_001271803.2:c.32+152C>T (chr5-138439392-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001271803.2(REEP2):c.32+152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 729,952 control chromosomes in the GnomAD database, including 19,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4831 hom., cov: 31)

Exomes 𝑓: 0.20 ( 14288 hom. )

Consequence

REEP2
NM_001271803.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Publications

2 publications found

Variant links:

Genes affected

REEP2 (HGNC:17975): (receptor accessory protein 2) This gene encodes a member of the receptor expression enhancing protein family. Studies of a related gene in mouse suggest that the encoded protein is found in the cell membrane and enhances the function of sweet taste receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

REEP2 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 72
Inheritance: AD, AR, SD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
hereditary spastic paraplegia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

REEP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 5-138439392-C-T is Benign according to our data. Variant chr5-138439392-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235420.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271803.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
REEP2	NM_001271803.2	MANE Select	c.32+152C>T	intron	N/A	NP_001258732.1	Q9BRK0-2
REEP2	NM_016606.4		c.32+152C>T	intron	N/A	NP_057690.2
REEP2	NR_073448.2		n.184+152C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
REEP2	ENST00000378339.7	TSL:1 MANE Select	c.32+152C>T	intron	N/A	ENSP00000367590.2	Q9BRK0-2
REEP2	ENST00000254901.9	TSL:1	c.32+152C>T	intron	N/A	ENSP00000254901.5	Q9BRK0-1
REEP2	ENST00000903314.1		c.32+152C>T	intron	N/A	ENSP00000573373.1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36322

AN:

151822

Hom.:

4825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.200

AC:

115499

AN:

578012

Hom.:

14288

AF XY:

0.198

AC XY:

60045

AN XY:

302978

show subpopulations

African (AFR)

AF:

0.281

AC:

3813

AN:

13556

American (AMR)

AF:

0.264

AC:

5558

AN:

21022

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

3727

AN:

12906

East Asian (EAS)

AF:

0.506

AC:

15059

AN:

29746

South Asian (SAS)

AF:

0.159

AC:

7942

AN:

50044

European-Finnish (FIN)

AF:

0.206

AC:

6615

AN:

32170

Middle Eastern (MID)

AF:

0.277

AC:

572

AN:

2064

European-Non Finnish (NFE)

AF:

0.170

AC:

65856

AN:

387856

Other (OTH)

AF:

0.222

AC:

6357

AN:

28648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4146

8292

12438

16584

20730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1258

2516

3774

5032

6290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

36337

AN:

151940

Hom.:

4831

Cov.:

AF XY:

0.243

AC XY:

18080

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.296

AC:

12275

AN:

41452

American (AMR)

AF:

0.255

AC:

3901

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

988

AN:

3468

East Asian (EAS)

AF:

0.551

AC:

2826

AN:

5132

South Asian (SAS)

AF:

0.181

AC:

874

AN:

4818

European-Finnish (FIN)

AF:

0.205

AC:

2167

AN:

10576

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12386

AN:

67914

Other (OTH)

AF:

0.256

AC:

539

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1357

2714

4070

5427

6784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.143

Hom.:

370

Bravo

AF:

0.251

Asia WGS

AF:

0.340

AC:

1182

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

1.2

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over