chr12-32740492-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012062.5(DNM1L):c.1968C>T(p.Leu656Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,430 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 44 hom., cov: 33)

Exomes 𝑓: 0.023 ( 473 hom. )

Consequence

DNM1L
NM_012062.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.150

Variant links:

Genes affected

DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

DNM1L links:

YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]

YARS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 12-32740492-C-T is Benign according to our data. Variant chr12-32740492-C-T is described in ClinVar as [Benign]. Clinvar id is 137128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0176 (2673/152262) while in subpopulation NFE AF= 0.0283 (1926/68016). AF 95% confidence interval is 0.0273. There are 44 homozygotes in gnomad4. There are 1277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2 link	c.2007C>T	p.Leu669Leu	synonymous_variant	Exon 19 of 21	ENST00000553257.6	NP_001265393.1	O00429-6B4DYR6
DNM1L	NM_012062.5 link	c.1968C>T	p.Leu656Leu	synonymous_variant	Exon 18 of 20	ENST00000549701.6	NP_036192.2	O00429-1B4DYR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6 link	c.2007C>T	p.Leu669Leu	synonymous_variant	Exon 19 of 21	2	NM_001278464.2	ENSP00000449089.1		O00429-6
DNM1L	ENST00000549701.6 link	c.1968C>T	p.Leu656Leu	synonymous_variant	Exon 18 of 20	1	NM_012062.5	ENSP00000450399.1		O00429-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2676

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00821

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0173

GnomAD3 exomes

AF:

0.0180

AC:

4515

AN:

250426

Hom.:

AF XY:

0.0187

AC XY:

2536

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00328

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00873

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0213

GnomAD4 exome

AF:

0.0227

AC:

33120

AN:

1461168

Hom.:

473

Cov.:

AF XY:

0.0225

AC XY:

16389

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.00367

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0338

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00953

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0258

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0176

AC:

2673

AN:

152262

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1277

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00428

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00821

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0230

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0299

EpiControl

AF:

0.0315

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 04, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.7

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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