rs1646022

Variant names:

• chr16-11276073-C-G
• rs1646022
• NM_002762.4:c.271+27G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-11276073-C-G
• chr16-11276073-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.784
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PRM2	NM_002762.4	c.271+27G>C		intron_variant	Intron 1 of 1	ENST00000241808.9	NP_002753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRM2	ENST00000241808.9	c.271+27G>C		intron_variant	Intron 1 of 1	1	NM_002762.4	ENSP00000241808.5

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

GnomAD2 exomes AF: 0.368 AC: 88367 AN: 240204 AF XY: 0.375

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 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

African (AFR) AF: 0.165 AC: 5536 AN: 33470

American (AMR) AF: 0.218 AC: 9701 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9079 AN: 26110

East Asian (EAS) AF: 0.289 AC: 11464 AN: 39668

South Asian (SAS) AF: 0.307 AC: 26461 AN: 86170

European-Finnish (FIN) AF: 0.449 AC: 22660 AN: 50524

Middle Eastern (MID) AF: 0.326 AC: 1880 AN: 5762

European-Non Finnish (NFE) AF: 0.463 AC: 513942 AN: 1111146

Other (OTH) AF: 0.409 AC: 24673 AN: 60290

GnomAD4 genome AF: 0.350 AC: 53276 AN: 152100 Hom.: 10512 Cov.: 33 AF XY: 0.345 AC XY: 25683 AN XY: 74372

African (AFR) AF: 0.178 AC: 7402 AN: 41508

American (AMR) AF: 0.296 AC: 4528 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1604 AN: 5158

South Asian (SAS) AF: 0.296 AC: 1429 AN: 4828

European-Finnish (FIN) AF: 0.449 AC: 4751 AN: 10584

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31055 AN: 67940

Other (OTH) AF: 0.354 AC: 749 AN: 2114

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

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	-0.88
CADD	Benign	0.36
DANN	Benign	0.61
PhyloP100		0.78
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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