1-111118189-G-C

Variant names:

• chr1-111118189-G-C
• NM_001349884.2:c.772C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001349884.2(DRAM2):​c.772C>G​(p.Arg258Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DRAM2 NM_001349884.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844

Genes affected

DRAM2 (HGNC:28769): (DNA damage regulated autophagy modulator 2) The protein encoded by this gene binds microtubule-associated protein 1 light chain 3 and is required for autophagy. Defects in this gene are a cause of retinal dystrophy. In addition, two microRNAs (microRNA 125b-1 and microRNA 144) can bind to the mRNA of this gene and produce the disease state. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0831306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRAM2	NM_001349884.2	c.772C>G	p.Arg258Gly	missense_variant	Exon 10 of 10	ENST00000484310.6	NP_001336813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRAM2	ENST00000484310.6	c.772C>G	p.Arg258Gly	missense_variant	Exon 10 of 10	1	NM_001349884.2	ENSP00000503400.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460916 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726766

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.044
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.26	T;T
Polyphen		0.21	B;B
Vest4		0.20
MutPred		0.33		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);
MVP		0.31
MPC		0.24
ClinPred		0.41	T
GERP RS		0.069
Varity_R		0.13
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-111660811;