Genetic Variant NM_001387844.1:c.8155A>G (chr1-171588461-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001387844.1(PRRC2C):c.8155A>G(p.Thr2719Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,613,710 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 96 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1213 hom. )

Consequence

PRRC2C
NM_001387844.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Publications

21 publications found

Variant links:

Genes affected

PRRC2C (HGNC:24903): (proline rich coiled-coil 2C) Enables protein C-terminus binding activity. Involved in stress granule assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PRRC2C 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 (MetaRNN=0.0018080473).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0282 (4291/152310) while in subpopulation SAS AF = 0.0433 (209/4824). AF 95% confidence interval is 0.0398. There are 96 homozygotes in GnomAd4. There are 2076 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 96 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2C	NM_001387844.1 link	c.8155A>G	p.Thr2719Ala	missense_variant	Exon 33 of 35	ENST00000647382.2	NP_001374773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2C	ENST00000647382.2 link	c.8155A>G	p.Thr2719Ala	missense_variant	Exon 33 of 35		NM_001387844.1	ENSP00000495867.2		Q9Y520-7A0A2R8YET2

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4288

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0425

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.0327

AC:

8207

AN:

250838

AF XY:

0.0345

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0287

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0506

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0389

AC:

56856

AN:

1461400

Hom.:

1213

Cov.:

AF XY:

0.0392

AC XY:

28499

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.00559

AC:

187

AN:

33474

American (AMR)

AF:

0.0147

AC:

658

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0313

AC:

819

AN:

26130

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0450

AC:

3881

AN:

86238

European-Finnish (FIN)

AF:

0.0497

AC:

2653

AN:

53400

Middle Eastern (MID)

AF:

0.0250

AC:

144

AN:

5768

European-Non Finnish (NFE)

AF:

0.0418

AC:

46498

AN:

1111630

Other (OTH)

AF:

0.0333

AC:

2012

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2723

5446

8168

10891

13614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1706

3412

5118

6824

8530

<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:

0.0282

AC:

4291

AN:

152310

Hom.:

Cov.:

AF XY:

0.0279

AC XY:

2076

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00604

AC:

251

AN:

41590

American (AMR)

AF:

0.0223

AC:

341

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

114

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0433

AC:

209

AN:

4824

European-Finnish (FIN)

AF:

0.0488

AC:

517

AN:

10602

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0411

AC:

2794

AN:

68028

Other (OTH)

AF:

0.0270

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0365

Hom.:

553

Bravo

AF:

0.0248

TwinsUK

AF:

0.0351

AC:

130

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0388

AC:

334

ExAC

AF:

0.0326

AC:

3952

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0039

T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

T;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.92

PhyloP100

3.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.64

N;N;.

REVEL

Benign

0.10

Sift

Benign

0.34

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0040

.;B;B

Vest4

0.050

MPC

0.20

ClinPred

0.0095

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.14

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over