16-11276248-GAC-TAT

Variant names:

• chr16-11276248-GAC-TAT
• NM_002762.4:c.121_123delGTCinsATA
• PRM2 p.Val41Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002762.4(PRM2):​c.121_123delGTCinsATA​(p.Val41Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V41F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRM2 NM_002762.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002762.4. 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.121_123delGTCinsATA	p.Val41Ile	missense	N/A	NP_002753.2	Q1LZN1
	PRM2	NM_001286356.2		c.121_123delGTCinsATA	p.Val41Ile	missense	N/A	NP_001273285.1	P04554-2
	PRM2	NM_001286358.2		c.121_123delGTCinsATA	p.Val41Ile	missense	N/A	NP_001273287.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM2	ENST00000241808.9	TSL:1 MANE Select	c.121_123delGTCinsATA	p.Val41Ile	missense	N/A	ENSP00000241808.5	P04554-1
	RMI2	ENST00000572173.1	TSL:1	c.-515-18968_-515-18966delGACinsTAT		intron	N/A	ENSP00000461206.1	Q96E14-2
	PRM2	ENST00000435245.2	TSL:2	c.121_123delGTCinsATA	p.Val41Ile	missense	N/A	ENSP00000403681.2	P04554-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-11370105;