Variant 16-11276073-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001286359.2(PRM2):c.298G>C(p.Ala100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,609,666 control chromosomes in the GnomAD database, including 149,388 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10512 hom., cov: 33)

Exomes 𝑓: 0.43 ( 138876 hom. )

Consequence

PRM2
NM_001286359.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.784

Variant links:

Genes affected

PRM2 (HGNC:9448): (protamine 2) Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis, and are the major DNA-binding proteins in the nucleus of sperm in many vertebrates. They package the sperm DNA into a highly condensed complex in a volume less than 5% of a somatic cell nucleus. Many mammalian species have only one protamine (protamine 1); however, a few species, including human and mouse, have two. This gene encodes protamine 2, which is cleaved to give rise to a family of protamine 2 peptides. Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Sep 2015]

PRM2 links:

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

RMI2 links:

RMI2 (HGNC:):

RMI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-11276073-C-G is Benign according to our data. Variant chr16-11276073-C-G is described in ClinVar as [Benign]. Clinvar id is 1272249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRM2	NM_002762.4 linkuse as main transcript	c.271+27G>C		intron_variant		ENST00000241808.9	NP_002753.2	P04554-1Q1LZN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRM2	ENST00000241808.9 linkuse as main transcript	c.271+27G>C		intron_variant		1	NM_002762.4	ENSP00000241808.5		P04554-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53273

AN:

151982

Hom.:

10511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.368

AC:

88367

AN:

240204

Hom.:

17614

AF XY:

0.375

AC XY:

49284

AN XY:

131278

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.429

AC:

625396

AN:

1457566

Hom.:

138876

Cov.:

AF XY:

0.428

AC XY:

310123

AN XY:

725078

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.409

GnomAD4 genome

AF:

0.350

AC:

53276

AN:

152100

Hom.:

10512

Cov.:

AF XY:

0.345

AC XY:

25683

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.328

Hom.:

1530

Bravo

AF:

0.331

Asia WGS

AF:

0.277

AC:

962

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.36

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over