DRAM2

DNA damage regulated autophagy modulator 2

Basic information

Region (hg38): 1:111117163-111140203

Previous symbols: [ "TMEM77" ]

Links

ENSG00000156171 ∙ NCBI:128338 ∙ OMIM:613360 ∙ HGNC:28769 ∙ Uniprot:Q6UX65 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy 21 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 21 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy 21	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	25983245

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DRAM2 gene.

• not provided (9 variants)
• Retinal dystrophy (7 variants)
• Cone-rod dystrophy 21 (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DRAM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				26		26
missense	3		76		1	80
nonsense	6		3			9
start loss	1					1
frameshift	3	1	2			6
inframe indel	2		2			4
splice donor/acceptor (+/-2bp)		4				4
splice region			4	10		14
non coding			3	24	5	32
Total	15	5	86	50	6

Highest pathogenic variant AF is 0.0000790

Variants in DRAM2

This is a list of pathogenic ClinVar variants found in the DRAM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-111118166-A-G			Likely benign (May 25, 2023)
1-111118182-C-T			Uncertain significance (Nov 08, 2022)
1-111118183-G-A			Benign (Jan 19, 2024)
1-111118189-G-A			Uncertain significance (Aug 16, 2022)
1-111118201-T-C			Uncertain significance (Aug 16, 2022)
1-111118202-AG-A			Uncertain significance (Jan 12, 2022)
1-111118216-T-G			Uncertain significance (Jul 07, 2022)
1-111118217-G-A			Likely benign (Oct 13, 2023)
1-111118217-G-C			Uncertain significance (Aug 23, 2022)
1-111118221-T-C			Uncertain significance (Jun 27, 2022)
1-111118221-T-G			Uncertain significance (Jul 12, 2022)
1-111118224-A-G		Cone-rod dystrophy 21 • Retinal dystrophy	Conflicting classifications of pathogenicity (Nov 01, 2024)
1-111118230-A-C			Uncertain significance (Sep 07, 2022)
1-111118234-C-T			Uncertain significance (May 12, 2022)
1-111118236-T-C			Uncertain significance (Jul 17, 2023)
1-111118242-T-C		Retinal dystrophy	Uncertain significance (Apr 28, 2022)
1-111118244-G-A			Likely benign (Oct 03, 2023)
1-111118250-C-A			Likely benign (Dec 18, 2022)
1-111118253-C-T			Likely benign (Jul 29, 2023)
1-111118254-C-T			Uncertain significance (Jan 15, 2022)
1-111118258-A-G			Likely benign (Dec 30, 2022)
1-111118260-G-T			Uncertain significance (Nov 14, 2023)
1-111118271-G-T		DRAM2-related disorder	Likely benign (Jul 29, 2020)
1-111118272-A-T		DRAM2-related disorder	Likely benign (Mar 17, 2020)
1-111118273-A-C		DRAM2-related disorder	Likely benign (Jul 29, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DRAM2	protein_coding	protein_coding	ENST00000286692	7	22884

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000136	0.865	125689	0	44	125733	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.454	126	141	0.893	0.00000707	1728
Missense in Polyphen		36	53.243	0.67615		693
Synonymous	-0.372	53	49.7	1.07	0.00000248	525
Loss of Function	1.37	8	13.4	0.597	5.65e-7	173

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000260	0.000255
Middle Eastern	0.0000557	0.0000544
South Asian	0.000364	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1. {ECO:0000269|PubMed:19895784, ECO:0000269|PubMed:25983245}.
• Disease: DISEASE: Cone-rod dystrophy 21 (CORD21) [MIM:616502]: A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:25983245}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0933

Intolerance Scores

• loftool: 0.644
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.106
• hipred: N
• hipred_score: 0.253
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dram2

Gene ontology

• Biological process: autophagy;apoptotic process;visual perception;regulation of autophagy;photoreceptor cell maintenance
• Cellular component: photoreceptor inner segment;cytoplasm;lysosome;lysosomal membrane;Golgi apparatus;integral component of membrane;apical plasma membrane;intracellular membrane-bounded organelle