Variant 16-2756450-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016333.4(SRRM2):c.86G>T(p.Arg29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SRRM2
NM_016333.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Variant links:

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 links:

SRRM2 (HGNC:):

SRRM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33222115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRM2	NM_016333.4 linkuse as main transcript	c.86G>T	p.Arg29Leu	missense_variant	2/15	ENST00000301740.13	NP_057417.3	Q9UQ35-1A0A140VK53
SRRM2	XM_047433882.1 linkuse as main transcript	c.167G>T	p.Arg56Leu	missense_variant	2/10		XP_047289838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRM2	ENST00000301740.13 linkuse as main transcript	c.86G>T	p.Arg29Leu	missense_variant	2/15	1	NM_016333.4	ENSP00000301740.8		Q9UQ35-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.86G>T (p.R29L) alteration is located in exon 2 (coding exon 1) of the SRRM2 gene. This alteration results from a G to T substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 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

Pathogenic

0.83

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.13

Sift4G

Uncertain

0.028

D;D;T

Polyphen

0.99

D;.;.

Vest4

0.24

MutPred

0.28

Loss of methylation at R29 (P = 0.0188);Loss of methylation at R29 (P = 0.0188);Loss of methylation at R29 (P = 0.0188);

MVP

0.49

ClinPred

0.81

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.71

gMVP

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over