16-11276090-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286359.2(PRM2):​c.281C>A​(p.Ala94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A94V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRM2 NM_001286359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>A		intron	N/A	NP_002753.2	Q1LZN1
	PRM2	NM_001286359.2		c.281C>A	p.Ala94Glu	missense	Exon 1 of 2	NP_001273288.1
	PRM2	NM_001286356.2		c.271+10C>A		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>A		intron	N/A	ENSP00000241808.5	P04554-1
	RMI2	ENST00000572173.1	TSL:1	c.-515-19126G>T		intron	N/A	ENSP00000461206.1	Q96E14-2
	PRM2	ENST00000435245.2	TSL:2	c.271+10C>A		intron	N/A	ENSP00000403681.2	P04554-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457082 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 724952

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44358

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.63
PhyloP100		-1.4
PromoterAI		-0.0032	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;