19-19004422-G-A

Variant names:

• chr19-19004422-G-A
• NM_001017392.5:c.2675C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017392.5(SUGP2):​c.2675C>T​(p.Pro892Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.950

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09053132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGP2	NM_001017392.5	c.2675C>T	p.Pro892Leu	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.2675C>T	p.Pro892Leu	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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2675C>T (p.P892L) alteration is located in exon 7 (coding exon 6) of the SUGP2 gene. This alteration results from a C to T substitution at nucleotide position 2675, causing the proline (P) at amino acid position 892 to be replaced by a leucine (L). 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	0.097
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.78	.;.;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.091	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;L;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.68	N;N;.;.
REVEL	Benign	0.015
Sift	Uncertain	0.012	D;D;.;.
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.24	B;B;B;.
Vest4		0.19
MutPred		0.21		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);.;
MVP		0.043
MPC		0.24
ClinPred		0.23	T
GERP RS		3.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.072
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-19115231;