Genetic Variant PRM2:p.Glu32Gln (chr16-11276277-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002762.4(PRM2):c.94G>C(p.Glu32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E32K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PRM2
NM_002762.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.113998055).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002762.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRM2	NM_002762.4	MANE Select	c.94G>C	p.Glu32Gln	missense	Exon 1 of 2	NP_002753.2	Q1LZN1
PRM2	NM_001286356.2		c.94G>C	p.Glu32Gln	missense	Exon 1 of 2	NP_001273285.1	P04554-2
PRM2	NM_001286358.2		c.94G>C	p.Glu32Gln	missense	Exon 1 of 2	NP_001273287.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRM2	ENST00000241808.9	TSL:1 MANE Select	c.94G>C	p.Glu32Gln	missense	Exon 1 of 2	ENSP00000241808.5	P04554-1
RMI2	ENST00000572173.1	TSL:1	c.-515-18939C>G		intron	N/A	ENSP00000461206.1	Q96E14-2
PRM2	ENST00000435245.2	TSL:2	c.94G>C	p.Glu32Gln	missense	Exon 1 of 2	ENSP00000403681.2	P04554-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.58

M_CAP

Benign

0.0032

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.15

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Benign

0.77

Polyphen

0.97

Vest4

0.10

MutPred

0.50

Loss of phosphorylation at S37 (P = 0.1575)

MVP

0.31

MPC

0.44

ClinPred

0.36

GERP RS

2.2

PromoterAI

0.0082

Neutral

(source)

Varity_R

0.26

gMVP

0.0069

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over