16-2756443-C-G

Position:

• chr16-2756443-C-G

Variant summary

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

The NM_016333.4(SRRM2):​c.79C>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRM2 NM_016333.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

SRRM2 (HGNC:16639): (serine/arginine repetitive matrix 2) Enables C2H2 zinc finger domain binding activity and protein N-terminus binding activity. Involved in mRNA splicing, via spliceosome. Located in Cajal body and nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Biomarker of Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

SRRM2 (HGNC:):

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
SRRM2	NM_016333.4	c.79C>G	p.Arg27Gly	missense_variant	2/15	ENST00000301740.13	NP_057417.3
SRRM2	XM_047433882.1	c.160C>G	p.Arg54Gly	missense_variant	2/10		XP_047289838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRM2	ENST00000301740.13	c.79C>G	p.Arg27Gly	missense_variant	2/15	1	NM_016333.4	ENSP00000301740.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.79C>G (p.R27G) alteration is located in exon 2 (coding exon 1) of the SRRM2 gene. This alteration results from a C to G substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a glycine (G). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.9	D;.;.
REVEL	Benign	0.25
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.84
MutPred		0.32		Loss of methylation at R27 (P = 0.0121);Loss of methylation at R27 (P = 0.0121);Loss of methylation at R27 (P = 0.0121);
MVP		0.47
ClinPred		0.95	D
GERP RS		3.2
Varity_R		0.85
gMVP		0.90

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: chr16-2806444;