chr2-227327572-C-G

Position:

• chr2-227327572-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277062.2(MFF):​c.-152-1106C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,146 control chromosomes in the GnomAD database, including 1,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.10 (1215 hom., cov: 33)
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.273

Genes affected

MFF (HGNC:24858): (mitochondrial fission factor) This is a nuclear gene encoding a protein that functions in mitochondrial and peroxisomal fission. The encoded protein recruits dynamin-1-like protein (DNM1L) to mitochondria. There are multiple pseudogenes for this gene on chromosomes 1, 5, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-227327572-C-G is Benign according to our data. Variant chr2-227327572-C-G is described in ClinVar as [Benign]. Clinvar id is 1263094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFF	NM_001277062.2	c.-152-1106C>G		intron_variant		ENST00000304593.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFF	ENST00000304593.14	c.-152-1106C>G		intron_variant		2	NM_001277062.2	P1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15125 AN: 152028 Hom.: 1215 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0806

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0995 AC: 15142 AN: 152146 Hom.: 1215 Cov.: 33 AF XY: 0.104 AC XY: 7770 AN XY: 74380

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0744 Hom.: 98

Bravo AF: 0.0993

Asia WGS AF: 0.100 AC: 346 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.40

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: rs7603414; hg19: chr2-228192288;