Genetic Variant CTTNBP2:p.Met1558Ile (chr7-117718090-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033427.3(CTTNBP2):c.4674G>C(p.Met1558Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CTTNBP2
NM_033427.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.522

Publications

0 publications found

Variant links:

Genes affected

CTTNBP2 (HGNC:15679): (cortactin binding protein 2) This gene encodes a protein with six ankyrin repeats and several proline-rich regions. A similar gene in rat interacts with a central regulator of the actin cytoskeleton. [provided by RefSeq, Jul 2008]

CTTNBP2 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CTTNBP2 links:

LOC105375469 (HGNC:):

LOC105375469 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06152129).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTTNBP2	NM_033427.3	MANE Select	c.4674G>C	p.Met1558Ile	missense	Exon 22 of 23	NP_219499.1	Q8WZ74
CTTNBP2	NM_001363349.1		c.4620G>C	p.Met1540Ile	missense	Exon 22 of 23	NP_001350278.1
CTTNBP2	NM_001363350.1		c.2577G>C	p.Met859Ile	missense	Exon 22 of 23	NP_001350279.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTTNBP2	ENST00000160373.8	TSL:1 MANE Select	c.4674G>C	p.Met1558Ile	missense	Exon 22 of 23	ENSP00000160373.3	Q8WZ74
CTTNBP2	ENST00000446636.5	TSL:5	c.3135G>C	p.Met1045Ile	missense	Exon 20 of 21	ENSP00000389576.1	H0Y448
CTTNBP2	ENST00000441556.5	TSL:5	n.*2588G>C		non_coding_transcript_exon	Exon 22 of 23	ENSP00000397678.1	F8WB16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250640

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460632

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111046

Other (OTH)

AF:

0.0000331

AC:

AN:

60344

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.2

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.020

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.64

M_CAP

Benign

0.011

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

PhyloP100

0.52

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.43

REVEL

Benign

0.11

Sift

Benign

0.42

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.20

MutPred

0.13

Loss of helix (P = 0.0558)

MVP

0.54

MPC

0.099

ClinPred

0.040

GERP RS

-0.79

Varity_R

0.082

gMVP

0.12

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over