rs8141797

Positions:

• chr22-24186073-A-G
• chr22-24186073-A-T

Variant summary

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

The NM_019601.4(SUSD2):​c.1397A>G​(p.Asn466Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,612,152 control chromosomes in the GnomAD database, including 4,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.097 (907 hom., cov: 33)
  • Exomes 𝑓: 0.067 (3822 hom.)
• Consequence: SUSD2 NM_019601.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.70

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050433874).
• BP6: Variant 22-24186073-A-G is Benign according to our data. Variant chr22-24186073-A-G is described in ClinVar as [Benign]. Clinvar id is 1255298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD2	NM_019601.4	c.1397A>G	p.Asn466Ser	missense_variant	9/15	ENST00000358321.4	NP_062547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD2	ENST00000358321.4	c.1397A>G	p.Asn466Ser	missense_variant	9/15	1	NM_019601.4	ENSP00000351075	P1
SUSD2	ENST00000463101.1	n.2290A>G		non_coding_transcript_exon_variant	7/11	2

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14678 AN: 152124 Hom.: 905 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0783

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0938

GnomAD3 exomes AF: 0.0807 AC: 20110 AN: 249124 Hom.: 981 AF XY: 0.0802 AC XY: 10836 AN XY: 135136

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0764

Gnomad ASJ exome AF: 0.0700

Gnomad EAS exome AF: 0.0940

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0820

Gnomad NFE exome AF: 0.0599

Gnomad OTH exome AF: 0.0745

GnomAD4 exome AF: 0.0675 AC: 98512 AN: 1459910 Hom.: 3822 Cov.: 32 AF XY: 0.0692 AC XY: 50213 AN XY: 726120

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0799

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.0939

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0794

Gnomad4 NFE exome AF: 0.0585

Gnomad4 OTH exome AF: 0.0699

GnomAD4 genome AF: 0.0966 AC: 14699 AN: 152242 Hom.: 907 Cov.: 33 AF XY: 0.0984 AC XY: 7323 AN XY: 74440

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0806

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0676 Hom.: 722

Bravo AF: 0.0983

TwinsUK AF: 0.0615 AC: 228

ALSPAC AF: 0.0509 AC: 196

ESP6500AA AF: 0.169 AC: 744

ESP6500EA AF: 0.0634 AC: 545

ExAC AF: 0.0819 AC: 9938

Asia WGS AF: 0.0910 AC: 317 AN: 3478

EpiCase AF: 0.0584

EpiControl AF: 0.0571

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	Nov 02, 2020	This variant is associated with the following publications: (PMID: 32620384) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.059
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.51	P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.11	T
Polyphen		0.57	P
Vest4		0.086
MPC		0.24
ClinPred		0.046	T
GERP RS		4.0
Varity_R		0.16
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs8141797; hg19: chr22-24582041; COSMIC: COSV64203069;