Genetic Variant NM_019601.4:c.1081G>A (chr22-24185671-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_019601.4(SUSD2):c.1081G>A(p.Gly361Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,609,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SUSD2
NM_019601.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Publications

1 publications found

Variant links:

Genes affected

SUSD2 (HGNC:30667): (sushi domain containing 2) Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of cell division. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUSD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUSD2	NM_019601.4 link	c.1081G>A	p.Gly361Ser	missense_variant	Exon 8 of 15	ENST00000358321.4	NP_062547.1	Q9UGT4A0A140VJW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUSD2	ENST00000358321.4 link	c.1081G>A	p.Gly361Ser	missense_variant	Exon 8 of 15	1	NM_019601.4	ENSP00000351075.3		Q9UGT4
SUSD2	ENST00000463101.1 link	n.1974G>A		non_coding_transcript_exon_variant	Exon 6 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000415

AC:

AN:

240896

AF XY:

0.0000304

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000931

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1457240

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

724466

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33418

American (AMR)

AF:

0.0000224

AC:

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00139

AC:

AN:

39600

South Asian (SAS)

AF:

0.00

AC:

AN:

85974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1110194

Other (OTH)

AF:

0.0000166

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000985

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000142

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000743

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1081G>A (p.G361S) alteration is located in exon 8 (coding exon 8) of the SUSD2 gene. This alteration results from a G to A substitution at nucleotide position 1081, causing the glycine (G) at amino acid position 361 to be replaced by a serine (S). 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

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.022

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

3.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.16

Sift

Uncertain

0.017

Sift4G

Uncertain

0.050

Polyphen

0.59

Vest4

0.23

MVP

0.19

MPC

0.29

ClinPred

0.18

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.66

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.47

Position offset: 2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over