22-24184807-C-G

Position:

• chr22-24184807-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000358321.4(SUSD2):​c.649C>G​(p.Leu217Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SUSD2 ENST00000358321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD2	NM_019601.4	c.649C>G	p.Leu217Val	missense_variant	5/15	ENST00000358321.4	NP_062547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD2	ENST00000358321.4	c.649C>G	p.Leu217Val	missense_variant	5/15	1	NM_019601.4	ENSP00000351075	P1
SUSD2	ENST00000463101.1	n.1542C>G		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249260 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459814 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 726150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.649C>G (p.L217V) alteration is located in exon 5 (coding exon 5) of the SUSD2 gene. This alteration results from a C to G substitution at nucleotide position 649, causing the leucine (L) at amino acid position 217 to be replaced by a valine (V). 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	0.27
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.016
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.41		Gain of methylation at K213 (P = 0.0615);
MVP		0.27
MPC		0.73
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1285097208; hg19: chr22-24580775;