16-11275998-G-T

Variant names:

• chr16-11275998-G-T
• rs2070923
• NM_002762.4:c.272-61C>A

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.06
• Publications: 16 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=-0.89).
• BP6: Variant 16-11275998-G-T is Benign according to our data. Variant chr16-11275998-G-T is described in ClinVar as Benign. ClinVar VariationId 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	c.272-61C>A		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.272-61C>A		intron_variant	Intron 1 of 1	1	NM_002762.4	ENSP00000241808.5

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48784 AN: 151040 Hom.: 8916 Cov.: 31

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

GnomAD2 exomes AF: 0.413 AC: 100014 AN: 242000 AF XY: 0.410

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 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.: 51 AF XY: 0.328 AC XY: 237625 AN XY: 723528

African (AFR) AF: 0.230 AC: 7674 AN: 33364

American (AMR) AF: 0.628 AC: 27949 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11949 AN: 25976

East Asian (EAS) AF: 0.706 AC: 28019 AN: 39664

South Asian (SAS) AF: 0.534 AC: 45894 AN: 86008

European-Finnish (FIN) AF: 0.311 AC: 16465 AN: 52896

Middle Eastern (MID) AF: 0.458 AC: 2634 AN: 5756

European-Non Finnish (NFE) AF: 0.278 AC: 307289 AN: 1105948

Other (OTH) AF: 0.338 AC: 20324 AN: 60144

GnomAD4 genome AF: 0.323 AC: 48837 AN: 151154 Hom.: 8943 Cov.: 31 AF XY: 0.335 AC XY: 24769 AN XY: 73860

African (AFR) AF: 0.227 AC: 9313 AN: 41094

American (AMR) AF: 0.488 AC: 7431 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1573 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3468 AN: 5112

South Asian (SAS) AF: 0.550 AC: 2638 AN: 4794

European-Finnish (FIN) AF: 0.318 AC: 3321 AN: 10434

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 19991 AN: 67736

Other (OTH) AF: 0.357 AC: 751 AN: 2106

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

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.67
PhyloP100		-2.1
PromoterAI		0.013	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: rs2070923; hg19: chr16-11369855;