rs1169826275

Variant names:

• chr1-111118217-G-A
• rs1169826275
• NM_001349884.2:c.744C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-111118217-G-A
• chr1-111118217-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001349884.2(DRAM2):​c.744C>T​(p.Asp248Asp) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRAM2 NM_001349884.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.350
• Publications: 0 publications found

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]

DRAM2 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 21

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-111118217-G-A is Benign according to our data. Variant chr1-111118217-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2128656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.35 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349884.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRAM2	NM_001349884.2	MANE Select	c.744C>T	p.Asp248Asp	synonymous	Exon 10 of 10	NP_001336813.1	Q6UX65
	DRAM2	NM_001349881.2		c.744C>T	p.Asp248Asp	synonymous	Exon 10 of 10	NP_001336810.1	Q6UX65
	DRAM2	NM_001349882.2		c.744C>T	p.Asp248Asp	synonymous	Exon 10 of 10	NP_001336811.1	Q6UX65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRAM2	ENST00000484310.6	TSL:1 MANE Select	c.744C>T	p.Asp248Asp	synonymous	Exon 10 of 10	ENSP00000503400.1	Q6UX65
	DRAM2	ENST00000286692.8	TSL:1	c.744C>T	p.Asp248Asp	synonymous	Exon 9 of 9	ENSP00000286692.4	Q6UX65
	DRAM2	ENST00000539140.6	TSL:1	c.744C>T	p.Asp248Asp	synonymous	Exon 9 of 9	ENSP00000437718.1	Q6UX65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.0
DANN	Benign	0.46
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs1169826275; hg19: chr1-111660839;