chr22-24186073-A-T

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_019601.4(SUSD2):​c.1397A>T​(p.Asn466Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N466S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUSD2 NM_019601.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

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>T	p.Asn466Ile	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>T	p.Asn466Ile	missense	Exon 9 of 15	ENSP00000351075.3
	SUSD2	ENST00000886473.1		c.1397A>T	p.Asn466Ile	missense	Exon 9 of 15	ENSP00000556532.1
	SUSD2	ENST00000959322.1		c.1397A>T	p.Asn466Ile	missense	Exon 9 of 15	ENSP00000629381.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460122 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726254

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111442

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.7
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.58		Loss of methylation at R468 (P = 0.0452)
MVP		0.73
MPC		0.81
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.89
gMVP		0.86
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs8141797; hg19: chr22-24582041;