rs2301365

Positions:

• chr16-11281429-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_933070.4(LOC105371082):​n.178+31651G>T variant causes a intron, non coding transcript 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: LOC105371082 XR_933070.4 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.956

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]

LOC105371082 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
LOC105371082	XR_933070.4	n.178+31651G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-515-13787G>T		intron_variant		1		ENSP00000461206
RMI2	ENST00000573910.1	n.160+31651G>T		intron_variant, non_coding_transcript_variant		3
RMI2	ENST00000649869.1	n.152+31651G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32640 AN: 152042 Hom.: 3928 Cov.: 33

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

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.: 33 AF XY: 0.214 AC XY: 15910 AN XY: 74376

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 27216534, 18390561) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs2301365; hg19: chr16-11375286;