Genetic Variant SURF2:p.Leu98Pro (chr9-133357770-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017503.5(SURF2):c.293T>C(p.Leu98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,613,668 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 1 hom. )

Consequence

SURF2
NM_017503.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18270898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SURF2	NM_017503.5 link	c.293T>C	p.Leu98Pro	missense_variant	Exon 3 of 6	ENST00000371964.5	NP_059973.4	Q15527
SURF2	NM_001278928.2 link	c.293T>C	p.Leu98Pro	missense_variant	Exon 3 of 6		NP_001265857.1	Q15527

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SURF2	ENST00000371964.5 link	c.293T>C	p.Leu98Pro	missense_variant	Exon 3 of 6	1	NM_017503.5	ENSP00000361032.4	Q15527
SURF2	ENST00000486887.1 link	n.195T>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
SURF2	ENST00000495524.5 link	n.474T>C		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000546

AC:

137

AN:

250734

Hom.:

AF XY:

0.000641

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000707

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000793

AC:

1159

AN:

1461424

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

581

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00108

Gnomad4 NFE exome

AF:

0.000886

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000506

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000620

Hom.:

Bravo

AF:

0.000536

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293T>C (p.L98P) alteration is located in exon 3 (coding exon 3) of the SURF2 gene. This alteration results from a T to C substitution at nucleotide position 293, causing the leucine (L) at amino acid position 98 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.82

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.70

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.33

Sift

Benign

0.12

Sift4G

Benign

0.15

Vest4

0.84

MVP

0.45

MPC

0.46

ClinPred

0.15

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over