Genetic Variant CSRP2:p.Glu54Lys (chr12-76863297-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001413541.1(CSRP2):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSRP2
NM_001413541.1 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

CSRP2 (HGNC:2470): (cysteine and glycine rich protein 2) CSRP2 is a member of the CSRP family of genes, encoding a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. CRP2 contains two copies of the cysteine-rich amino acid sequence motif (LIM) with putative zinc-binding activity, and may be involved in regulating ordered cell growth. Other genes in the family include CSRP1 and CSRP3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CSRP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 14 codons. Genomic position: 76863260. Lost 0.079 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413541.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSRP2	NM_001321.3	MANE Select	c.160G>A	p.Glu54Lys	missense	Exon 3 of 6	NP_001312.1	Q16527
CSRP2	NM_001413541.1		c.3G>A	p.Met1?	start_lost	Exon 3 of 7	NP_001400470.1
CSRP2	NM_001413539.1		c.160G>A	p.Glu54Lys	missense	Exon 3 of 7	NP_001400468.1	F8VW96

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSRP2	ENST00000311083.10	TSL:1 MANE Select	c.160G>A	p.Glu54Lys	missense	Exon 3 of 6	ENSP00000310901.5	Q16527
CSRP2	ENST00000548783.1	TSL:1	n.1658G>A		non_coding_transcript_exon	Exon 1 of 3
CSRP2	ENST00000919909.1		c.160G>A	p.Glu54Lys	missense	Exon 3 of 7	ENSP00000589968.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

-0.12

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.49

PhyloP100

1.4

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.70

REVEL

Uncertain

0.30

Sift

Benign

0.66

Sift4G

Benign

0.63

Polyphen

0.0050

Vest4

0.37

MutPred

0.72

Gain of methylation at E54 (P = 0.0124)

MVP

0.93

MPC

0.35

ClinPred

0.34

GERP RS

5.8

Varity_R

0.17

gMVP

0.37

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over