NM_002762.4:c.185G>A

Variant names:

• chr16-11276186-C-T
• NM_002762.4:c.185G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002762.4(PRM2):​c.185G>A​(p.Arg62Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRM2 NM_002762.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

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]

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]

LOC105371082 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19330329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRM2	NM_002762.4	c.185G>A	p.Arg62Lys	missense_variant	Exon 1 of 2	ENST00000241808.9	NP_002753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRM2	ENST00000241808.9	c.185G>A	p.Arg62Lys	missense_variant	Exon 1 of 2	1	NM_002762.4	ENSP00000241808.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.94	P;.
Vest4		0.27
MutPred		0.58		Gain of methylation at R62 (P = 0.016);Gain of methylation at R62 (P = 0.016);
MVP		0.14
MPC		0.13
ClinPred		0.92	D
GERP RS		3.3
Varity_R		0.56
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-11370043;