chr12-32731020-T-C

Variant names:

• chr12-32731020-T-C
• NM_001278464.2:c.1125T>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_012062.5(DNM1L):​c.1086T>C​(p.Gly362Gly) 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: 33)
• Consequence: DNM1L NM_012062.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198
• Publications: 0 publications found

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]

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 Gene-Disease associations (from GenCC):

• myopathy, lactic acidosis, and sideroblastic anemia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• myopathy, lactic acidosis, and sideroblastic anemia

  Inheritance: AR 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=-0.52).
• BP6: Variant 12-32731020-T-C is Benign according to our data. Variant chr12-32731020-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3620017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012062.5. 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
	DNM1L	NM_001278464.2	MANE Plus Clinical	c.1125T>C	p.Gly375Gly	synonymous	Exon 11 of 21	NP_001265393.1	O00429-6
	DNM1L	NM_012062.5	MANE Select	c.1086T>C	p.Gly362Gly	synonymous	Exon 10 of 20	NP_036192.2	O00429-1
	DNM1L	NM_001278465.2		c.1125T>C	p.Gly375Gly	synonymous	Exon 11 of 20	NP_001265394.1	O00429-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1L	ENST00000553257.6	TSL:2 MANE Plus Clinical	c.1125T>C	p.Gly375Gly	synonymous	Exon 11 of 21	ENSP00000449089.1	O00429-6
	DNM1L	ENST00000549701.6	TSL:1 MANE Select	c.1086T>C	p.Gly362Gly	synonymous	Exon 10 of 20	ENSP00000450399.1	O00429-1
	DNM1L	ENST00000381000.8	TSL:1	c.1125T>C	p.Gly375Gly	synonymous	Exon 11 of 20	ENSP00000370388.4	O00429-8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	-0.52
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr12-32883954;