2-135709594-C-G

Variant names:

• chr2-135709594-C-G
• rs2304367
• NM_001378107.1:c.2563+58C>G

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2563+58C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 7 publications found

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308733 (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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2563+58C>G		intron_variant	Intron 22 of 26	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2563+58C>G		intron_variant	Intron 22 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1433760 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 712940

African (AFR) AF: 0.00 AC: 0 AN: 32300

American (AMR) AF: 0.00 AC: 0 AN: 40610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.00 AC: 0 AN: 83840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094502

Other (OTH) AF: 0.00 AC: 0 AN: 59300

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2304367; hg19: chr2-136467164;