rs1646022

chr16-11276073-C-Gchr16-11276073-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002762.4(PRM2):c.271+27G>C variant causes a intron 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. 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_002762.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.784

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 Benign. Variant got -14 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_single_submitter, 1 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	UniProt
PRM2	NM_002762.4	c.271+27G>C		intron_variant		ENST00000241808.9
LOC105371082	XR_933070.4	n.178+26295C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRM2	ENST00000241808.9	c.271+27G>C		intron_variant		1	NM_002762.4	P2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53273 AN: 151982 Hom.: 10511 Cov.: 33

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

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.: 70 AF XY: 0.428 AC XY: 310123 AN XY: 725078

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.: 33 AF XY: 0.345 AC XY: 25683 AN XY: 74372

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs1646022; hg19: chr16-11369930; COSMIC: COSV54113633; COSMIC: COSV54113633;