1-111118254-C-G

Variant names:

• chr1-111118254-C-G
• rs765482763
• NM_001349884.2:c.707G>C

Variant summary

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

The NM_001349884.2(DRAM2):​c.707G>C​(p.Arg236Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRAM2 NM_001349884.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRAM2	NM_001349884.2	c.707G>C	p.Arg236Pro	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.707G>C	p.Arg236Pro	missense_variant	Exon 10 of 10	1	NM_001349884.2	ENSP00000503400.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248322 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.55		Gain of methylation at K232 (P = 0.039);Gain of methylation at K232 (P = 0.039);
MVP		0.38
MPC		0.56
ClinPred		0.97	D
GERP RS		0.57
Varity_R		0.49
gMVP		0.87

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

LitVar

Other links and lift over

dbSNP: rs765482763; hg19: chr1-111660876;