rs8141797

Variant names:

• chr22-24186073-A-G
• rs8141797
• NM_019601.4:c.1397A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 62 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019601.4. 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
	SUSD2	NM_019601.4	MANE Select	c.1397A>G	p.Asn466Ser	missense	Exon 9 of 15	NP_062547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD2	ENST00000358321.4	TSL:1 MANE Select	c.1397A>G	p.Asn466Ser	missense	Exon 9 of 15	ENSP00000351075.3
	SUSD2	ENST00000886473.1		c.1397A>G	p.Asn466Ser	missense	Exon 9 of 15	ENSP00000556532.1
	SUSD2	ENST00000959322.1		c.1397A>G	p.Asn466Ser	missense	Exon 9 of 15	ENSP00000629381.1

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

GnomAD2 exomes AF: 0.0807 AC: 20110 AN: 249124 AF XY: 0.0802

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 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

African (AFR) AF: 0.168 AC: 5636 AN: 33452

American (AMR) AF: 0.0799 AC: 3567 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 1916 AN: 26108

East Asian (EAS) AF: 0.0939 AC: 3724 AN: 39668

South Asian (SAS) AF: 0.112 AC: 9697 AN: 86196

European-Finnish (FIN) AF: 0.0794 AC: 4161 AN: 52404

Middle Eastern (MID) AF: 0.101 AC: 580 AN: 5762

European-Non Finnish (NFE) AF: 0.0585 AC: 65015 AN: 1111334

Other (OTH) AF: 0.0699 AC: 4216 AN: 60346

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

African (AFR) AF: 0.166 AC: 6904 AN: 41560

American (AMR) AF: 0.0792 AC: 1212 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3468

East Asian (EAS) AF: 0.0787 AC: 407 AN: 5170

South Asian (SAS) AF: 0.118 AC: 571 AN: 4822

European-Finnish (FIN) AF: 0.0806 AC: 855 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4212 AN: 67996

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.0722 Hom.: 1797

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.7
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
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8141797; hg19: chr22-24582041; COSMIC: COSV64203069;