12-32679350-G-A

Variant names:

• chr12-32679350-G-A
• rs201968952
• NM_001278464.2:c.-14G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_012062.5(DNM1L):​c.-14G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,605,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: DNM1L NM_012062.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.868

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-32679350-G-A is Benign according to our data. Variant chr12-32679350-G-A is described in ClinVar as [Benign]. Clinvar id is 214307.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00148 (226/152306) while in subpopulation AFR AF= 0.00529 (220/41562). AF 95% confidence interval is 0.00472. There are 1 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2	c.-14G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 21	ENST00000553257.6	NP_001265393.1
DNM1L	NM_012062.5	c.-14G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 20	ENST00000549701.6	NP_036192.2
DNM1L	NM_001278464.2	c.-14G>A		5_prime_UTR_variant	Exon 1 of 21	ENST00000553257.6	NP_001265393.1
DNM1L	NM_012062.5	c.-14G>A		5_prime_UTR_variant	Exon 1 of 20	ENST00000549701.6	NP_036192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257	c.-14G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 21	2	NM_001278464.2	ENSP00000449089.1
DNM1L	ENST00000549701	c.-14G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 20	1	NM_012062.5	ENSP00000450399.1
DNM1L	ENST00000553257	c.-14G>A		5_prime_UTR_variant	Exon 1 of 21	2	NM_001278464.2	ENSP00000449089.1
DNM1L	ENST00000549701	c.-14G>A		5_prime_UTR_variant	Exon 1 of 20	1	NM_012062.5	ENSP00000450399.1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 226 AN: 152186 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000380 AC: 93 AN: 244736 Hom.: 0 AF XY: 0.000248 AC XY: 33 AN XY: 132920

Gnomad AFR exome AF: 0.00574

Gnomad AMR exome AF: 0.0000881

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000142 AC: 206 AN: 1452840 Hom.: 1 Cov.: 29 AF XY: 0.000131 AC XY: 95 AN XY: 723198

Gnomad4 AFR exome AF: 0.00549

Gnomad4 AMR exome AF: 0.0000900

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000362

Gnomad4 OTH exome AF: 0.000233

GnomAD4 genome AF: 0.00148 AC: 226 AN: 152306 Hom.: 1 Cov.: 33 AF XY: 0.00119 AC XY: 89 AN XY: 74480

Gnomad4 AFR AF: 0.00529

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.00158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 23, 2015

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	-0.79
CADD	Benign	8.6
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs201968952; hg19: chr12-32832284;