16-11276090-G-A

Variant names:

• chr16-11276090-G-A
• rs74007626
• NM_002762.4:c.271+10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001286359.2(PRM2):​c.281C>T​(p.Ala94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,609,342 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (217 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (200 hom.)
• Consequence: PRM2 NM_001286359.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41
• Publications: 3 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=-0.93).
• BP6: Variant 16-11276090-G-A is Benign according to our data. Variant chr16-11276090-G-A is described in ClinVar as Benign. ClinVar VariationId is 776978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286359.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM2	NM_002762.4	MANE Select	c.271+10C>T		intron	N/A	NP_002753.2	Q1LZN1
	PRM2	NM_001286359.2		c.281C>T	p.Ala94Val	missense	Exon 1 of 2	NP_001273288.1
	PRM2	NM_001286356.2		c.271+10C>T		intron	N/A	NP_001273285.1	P04554-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM2	ENST00000241808.9	TSL:1 MANE Select	c.271+10C>T		intron	N/A	ENSP00000241808.5	P04554-1
	RMI2	ENST00000572173.1	TSL:1	c.-515-19126G>A		intron	N/A	ENSP00000461206.1	Q96E14-2
	PRM2	ENST00000435245.2	TSL:2	c.271+10C>T		intron	N/A	ENSP00000403681.2	P04554-2

Frequencies

GnomAD3 genomes AF: 0.0292 AC: 4450 AN: 152144 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00733 AC: 1741 AN: 237658 AF XY: 0.00552

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00373

GnomAD4 exome AF: 0.00300 AC: 4376 AN: 1457080 Hom.: 200 Cov.: 36 AF XY: 0.00264 AC XY: 1914 AN XY: 724950

African (AFR) AF: 0.104 AC: 3492 AN: 33472

American (AMR) AF: 0.00478 AC: 212 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49748

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5760

European-Non Finnish (NFE) AF: 0.000130 AC: 145 AN: 1111494

Other (OTH) AF: 0.00680 AC: 410 AN: 60292

GnomAD4 genome AF: 0.0293 AC: 4463 AN: 152262 Hom.: 217 Cov.: 33 AF XY: 0.0285 AC XY: 2122 AN XY: 74456

African (AFR) AF: 0.103 AC: 4261 AN: 41516

American (AMR) AF: 0.00856 AC: 131 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68004

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0223 Hom.: 16

Bravo AF: 0.0328

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.85
PhyloP100		-1.4
PromoterAI		-0.0028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74007626; hg19: chr16-11369947; COSMIC: COSV54113268; COSMIC: COSV54113268;