rs2275813

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198576.4(AGRN):​c.4745-17C>G variant causes a splice polypyrimidine tract, intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

AGRN
NM_198576.4 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75
Variant links:
Genes affected
AGRN (HGNC:329): (agrin) This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

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ACMG classification

Classification made for transcript

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 (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGRNNM_198576.4 linkuse as main transcriptc.4745-17C>G splice_polypyrimidine_tract_variant, intron_variant ENST00000379370.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGRNENST00000379370.7 linkuse as main transcriptc.4745-17C>G splice_polypyrimidine_tract_variant, intron_variant 1 NM_198576.4 P1O00468-6
AGRNENST00000620552.4 linkuse as main transcriptc.4331-17C>G splice_polypyrimidine_tract_variant, intron_variant 5
AGRNENST00000651234.1 linkuse as main transcriptc.4430-17C>G splice_polypyrimidine_tract_variant, intron_variant
AGRNENST00000652369.1 linkuse as main transcriptc.4430-17C>G splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
86
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.19
DANN
Benign
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs2275813; hg19: chr1-985266; API