dbSNP rs2301365: RMI2:c.-515-13787G>T (chr16-11281429-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000572173.1(RMI2):c.-515-13787G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 644,152 control chromosomes in the GnomAD database, including 18,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3926 hom., cov: 33)

Exomes 𝑓: 0.24 ( 15000 hom. )

Consequence

RMI2
ENST00000572173.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.956

Variant links:

Genes affected

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]

RMI2 links:

LOC105371082 (HGNC:):

LOC105371082 links:

PRM1 (HGNC:9447): (protamine 1) Predicted to enable DNA binding activity. Predicted to be involved in DNA packaging. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-11281429-G-T is Benign according to our data. Variant chr16-11281429-G-T is described in ClinVar as [Benign]. Clinvar id is 1223123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4 link	n.178+31651G>T		intron_variant	Intron 1 of 2
PRM1	NM_002761.3 link	c.-191C>A		upstream_gene_variant		ENST00000312511.4	NP_002752.1	P04553Q3MN80

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RMI2	ENST00000572173.1 link	c.-515-13787G>T	intron_variant	Intron 1 of 4	1		ENSP00000461206.1	Q96E14-2
RMI2	ENST00000573910.1 link	n.160+31651G>T	intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1 link	n.152+31651G>T	intron_variant	Intron 1 of 2
PRM1	ENST00000312511.4 link	c.-191C>A	upstream_gene_variant		1	NM_002761.3	ENSP00000310515.3	P04553

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32640

AN:

152042

Hom.:

3928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.239

AC:

117650

AN:

491992

Hom.:

15000

AF XY:

0.237

AC XY:

62048

AN XY:

261816

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.214

AC:

32627

AN:

152160

Hom.:

3926

Cov.:

AF XY:

0.214

AC XY:

15910

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.237

Hom.:

586

Bravo

AF:

0.200

Asia WGS

AF:

0.202

AC:

699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27216534, 18390561) -

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

-0.85

CADD

Benign

0.066

DANN

Benign

0.52

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over