dbSNP rs17318596: DMAC2:c.*1041C>T (chr19-41431190-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018035.3(DMAC2):c.*1041C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 518,682 control chromosomes in the GnomAD database, including 38,178 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9188 hom., cov: 32)

Exomes 𝑓: 0.39 ( 28990 hom. )

Consequence

DMAC2
NM_018035.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

76 publications found

Variant links:

COSMIC-nc: COSV55729421

Genes affected

DMAC2 (HGNC:25496): (distal membrane arm assembly component 2) Involved in mitochondrial respiratory chain complex I assembly. Colocalizes with mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

DMAC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAC2	NM_018035.3 link	c.*1041C>T		downstream_gene_variant		ENST00000221943.14	NP_060505.2	Q9NW81-1A0A024R0K4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DMAC2	ENST00000221943.14 link	c.*1041C>T	downstream_gene_variant	2	NM_018035.3	ENSP00000221943.8	Q9NW81-1
DMAC2	ENST00000438807.7 link	c.*1094C>T	downstream_gene_variant	1		ENSP00000397413.3	Q9NW81-2
DMAC2	ENST00000592922.6 link	c.*1041C>T	downstream_gene_variant	2		ENSP00000467205.1	Q9NW81-5
DMAC2	ENST00000589503.1 link	n.*129C>T	downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50488

AN:

151862

Hom.:

9174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.347

GnomAD2 exomes

AF:

0.398

AC:

91165

AN:

229234

AF XY:

0.396

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.391

AC:

143302

AN:

366702

Hom.:

28990

Cov.:

AF XY:

0.392

AC XY:

82463

AN XY:

210264

show subpopulations

African (AFR)

AF:

0.196

AC:

2056

AN:

10510

American (AMR)

AF:

0.506

AC:

18356

AN:

36302

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

4396

AN:

11744

East Asian (EAS)

AF:

0.559

AC:

7357

AN:

13172

South Asian (SAS)

AF:

0.409

AC:

27287

AN:

66766

European-Finnish (FIN)

AF:

0.340

AC:

5745

AN:

16910

Middle Eastern (MID)

AF:

0.355

AC:

1012

AN:

2852

European-Non Finnish (NFE)

AF:

0.370

AC:

70971

AN:

191836

Other (OTH)

AF:

0.369

AC:

6122

AN:

16610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

6765

13529

20294

27058

33823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.333

AC:

50537

AN:

151980

Hom.:

9188

Cov.:

AF XY:

0.336

AC XY:

24959

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.197

AC:

8164

AN:

41460

American (AMR)

AF:

0.423

AC:

6449

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1288

AN:

3470

East Asian (EAS)

AF:

0.560

AC:

2894

AN:

5168

South Asian (SAS)

AF:

0.404

AC:

1944

AN:

4814

European-Finnish (FIN)

AF:

0.330

AC:

3484

AN:

10548

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.372

AC:

25288

AN:

67960

Other (OTH)

AF:

0.350

AC:

738

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1633

3265

4898

6530

8163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.363

Hom.:

39419

Bravo

AF:

0.334

Asia WGS

AF:

0.465

AC:

1619

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Pathogenic

0.15

CADD

Benign

0.045

(source)

DANN

Benign

0.90

PhyloP100

-2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over