19-19004536-C-G

Variant names:

• chr19-19004536-C-G
• NM_001017392.5:c.2561G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001017392.5(SUGP2):​c.2561G>C​(p.Gly854Ala) 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: SUGP2 NM_001017392.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.747

Genes affected

SUGP2 (HGNC:18641): (SURP and G-patch domain containing 2) This gene encodes a member of the arginine/serine-rich family of splicing factors. The encoded protein functions in mRNA processing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049699515).
• BP6: Variant 19-19004536-C-G is Benign according to our data. Variant chr19-19004536-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3451177.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGP2	NM_001017392.5	c.2561G>C	p.Gly854Ala	missense_variant	Exon 7 of 11	ENST00000452918.7	NP_001017392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUGP2	ENST00000452918.7	c.2561G>C	p.Gly854Ala	missense_variant	Exon 7 of 11	1	NM_001017392.5	ENSP00000389380.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 26, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.089
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.41
DANN	Benign	0.069
DEOGEN2	Benign	0.0030	T;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.56	.;.;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N;N;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.36	N;N;.;.
REVEL	Benign	0.026
Sift	Benign	0.64	T;T;.;.
Sift4G	Benign	0.84	T;T;T;T
Polyphen		0.23	B;B;B;.
Vest4		0.028
MutPred		0.13		Gain of catalytic residue at G854 (P = 0.0266);Gain of catalytic residue at G854 (P = 0.0266);Gain of catalytic residue at G854 (P = 0.0266);.;
MVP		0.082
MPC		0.21
ClinPred		0.050	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.031
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-19115345;