Genetic Variant SURF2:c.78+104_78+110dupGGGAGAG (chr9-133356757-C-CAGGGGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017503.5(SURF2):c.78+104_78+110dupGGGAGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,340,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SURF2
NM_017503.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

0 publications found

Variant links:

Genes affected

SURF2 (HGNC:11475): (surfeit 2) This gene shares a bidirectional promoter with surfeit 1 (SURF1; GeneID: 6834), which is located on the opposite strand. It encodes a conserved protein that is expressed in a variety of tissues. [provided by RefSeq, Jul 2013]

SURF2 links:

SURF1 (HGNC:11474): (SURF1 cytochrome c oxidase assembly factor) This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency. [provided by RefSeq, Jul 2008]

SURF1 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
mitochondrial complex IV deficiency, nuclear type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease type 4K
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
Leigh syndrome with cardiomyopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SURF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017503.5. 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
	SURF2	NM_017503.5	MANE Select	c.78+104_78+110dupGGGAGAG		intron	N/A	NP_059973.4
	SURF2	NM_001278928.2		c.78+104_78+110dupGGGAGAG		intron	N/A	NP_001265857.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SURF2	ENST00000371964.5	TSL:1 MANE Select	c.78+104_78+110dupGGGAGAG	intron	N/A	ENSP00000361032.4	Q15527
SURF2	ENST00000934438.1		c.78+104_78+110dupGGGAGAG	intron	N/A	ENSP00000604497.1
SURF2	ENST00000875735.1		c.78+104_78+110dupGGGAGAG	intron	N/A	ENSP00000545794.1

Frequencies

GnomAD3 genomes

AF:

0.0000213

AC:

AN:

140834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000610

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

148

AN:

1199314

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

584808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25666

American (AMR)

AF:

0.00

AC:

AN:

23194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18852

East Asian (EAS)

AF:

0.00435

AC:

137

AN:

31498

South Asian (SAS)

AF:

0.0000159

AC:

AN:

62790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3492

European-Non Finnish (NFE)

AF:

0.00000839

AC:

AN:

953334

Other (OTH)

AF:

0.0000397

AC:

AN:

50416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000213

AC:

AN:

140834

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

68112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37426

American (AMR)

AF:

0.00

AC:

AN:

13908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3368

East Asian (EAS)

AF:

0.000610

AC:

AN:

4920

South Asian (SAS)

AF:

0.00

AC:

AN:

4434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64786

Other (OTH)

AF:

0.00

AC:

AN:

1940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.061

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-133356757-CAGGGGAGAGGGGAG-CAGGGGAGAGGGGAGAGGGGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over