Genetic Variant PRM2:c.272-61C>A (chr16-11275998-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002762.4(PRM2):c.272-61C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,605,386 control chromosomes in the GnomAD database, including 94,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8943 hom., cov: 31)

Exomes 𝑓: 0.32 ( 85111 hom. )

Consequence

PRM2
NM_002762.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.06

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:

LOC105371082 (HGNC:):

LOC105371082 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=-0.89).

BP6

Variant 16-11275998-G-T is Benign according to our data. Variant chr16-11275998-G-T is described in ClinVar as [Benign]. Clinvar id is 1289745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRM2	NM_002762.4 link	c.272-61C>A		intron_variant	Intron 1 of 1	ENST00000241808.9	NP_002753.2	P04554-1Q1LZN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRM2	ENST00000241808.9 link	c.272-61C>A		intron_variant	Intron 1 of 1	1	NM_002762.4	ENSP00000241808.5		P04554-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

48784

AN:

151040

Hom.:

8916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.413

AC:

100014

AN:

242000

Hom.:

23786

AF XY:

0.410

AC XY:

54000

AN XY:

131550

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.535

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.322

AC:

468197

AN:

1454232

Hom.:

85111

Cov.:

AF XY:

0.328

AC XY:

237625

AN XY:

723528

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.628

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.706

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.323

AC:

48837

AN:

151154

Hom.:

8943

Cov.:

AF XY:

0.335

AC XY:

24769

AN XY:

73860

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.550

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.247

Hom.:

940

Bravo

AF:

0.333

Asia WGS

AF:

0.582

AC:

2020

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.52

DANN

Benign

0.67

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