2-227328648-T-G

Position:

• chr2-227328648-T-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.-152-30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 151,924 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (381 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11

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=-0.6).
• BP6: Variant 2-227328648-T-G is Benign according to our data. Variant chr2-227328648-T-G is described in ClinVar as [Benign]. Clinvar id is 1271167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-152-30T>G		intron_variant		ENST00000304593.14	NP_001263991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14	c.-152-30T>G		intron_variant		2	NM_001277062.2	ENSP00000304898	P1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6737 AN: 151806 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0295

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00302

Gnomad OTH AF: 0.0365

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0444 AC: 6746 AN: 151924 Hom.: 381 Cov.: 32 AF XY: 0.0463 AC XY: 3441 AN XY: 74300

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0249 Hom.: 26

Bravo AF: 0.0469

Asia WGS AF: 0.0850 AC: 293 AN: 3478

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	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs77362510; hg19: chr2-228193364;