22-24183628-G-T

Position:

• chr22-24183628-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_019601.4(SUSD2):​c.421G>T​(p.Ala141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUSD2 NM_019601.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08852026).
• BP6: Variant 22-24183628-G-T is Benign according to our data. Variant chr22-24183628-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3172271.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD2	NM_019601.4	c.421G>T	p.Ala141Ser	missense_variant	3/15	ENST00000358321.4	NP_062547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD2	ENST00000358321.4	c.421G>T	p.Ala141Ser	missense_variant	3/15	1	NM_019601.4	ENSP00000351075	P1
SUSD2	ENST00000463101.1	n.825G>T		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.13
DANN	Benign	0.87
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.19	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.025
Sift	Benign	0.92	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.029
MutPred		0.49		Loss of sheet (P = 7e-04);
MVP		0.061
MPC		0.16
ClinPred		0.072	T
GERP RS		-0.065
Varity_R		0.029
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24579596;