Variant 1-111118183-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM1BP4_StrongBP6_ModerateBS1BS2

The ENST00000484310.6(DRAM2):c.778C>T(p.Arg260Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,612,794 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R260Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 8 hom. )

Consequence

DRAM2
ENST00000484310.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PM1

In a chain DNA damage-regulated autophagy modulator protein 2 (size 265) in uniprot entity DRAM2_HUMAN there are 8 pathogenic changes around while only 2 benign (80%) in ENST00000484310.6

BP4

Computational evidence support a benign effect (MetaRNN=0.004404843).

BP6

Variant 1-111118183-G-A is Benign according to our data. Variant chr1-111118183-G-A is described in ClinVar as [Benign]. Clinvar id is 786853.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00311 (473/152050) while in subpopulation AFR AF= 0.011 (456/41538). AF 95% confidence interval is 0.0101. There are 3 homozygotes in gnomad4. There are 217 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRAM2	NM_001349884.2 linkuse as main transcript	c.778C>T	p.Arg260Trp	missense_variant	10/10	ENST00000484310.6	NP_001336813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRAM2	ENST00000484310.6 linkuse as main transcript	c.778C>T	p.Arg260Trp	missense_variant	10/10	1	NM_001349884.2	ENSP00000503400	P1

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

473

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000919

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000888

AC:

223

AN:

251036

Hom.:

AF XY:

0.000663

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000345

AC:

504

AN:

1460744

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

215

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.000582

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00311

AC:

473

AN:

152050

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

217

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00374

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00114

AC:

139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.12

Sift

Benign

0.19

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;B

Vest4

0.071

MVP

0.31

MPC

0.14

ClinPred

0.036

GERP RS

2.9

Varity_R

0.038

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over