Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000333244.6(AHNAK2):c.4274A>G(p.Asp1425Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 18)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AHNAK2
ENST00000333244.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.791

Publications

0 publications found

Variant links:

Genes affected

AHNAK2 (HGNC:20125): (AHNAK nucleoprotein 2) This gene encodes a large nucleoprotein. The encoded protein has a tripartite domain structure with a relatively short N-terminus and a long C-terminus, separated by a large body of repeats. The N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain is thought to function in the formation of stable homodimers. The encoded protein may play a role in calcium signaling by associating with calcium channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

AHNAK2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease
Inheritance: AR Classification: LIMITED Submitted by: Illumina, Ambry Genetics

AHNAK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.08043274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000333244.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHNAK2	NM_138420.4	MANE Select	c.4274A>G	p.Asp1425Gly	missense	Exon 7 of 7	NP_612429.2
	AHNAK2	NM_001350929.2		c.3974A>G	p.Asp1325Gly	missense	Exon 7 of 7	NP_001337858.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AHNAK2	ENST00000333244.6	TSL:5 MANE Select	c.4274A>G	p.Asp1425Gly	missense	Exon 7 of 7	ENSP00000353114.4
AHNAK2	ENST00000557457.1	TSL:1	c.-221+2704A>G		intron	N/A	ENSP00000450998.1
AHNAK2	ENST00000555122.1	TSL:5	n.4402A>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

964146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

478744

African (AFR)

AF:

0.00

AC:

AN:

31810

American (AMR)

AF:

0.00

AC:

AN:

36348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14148

East Asian (EAS)

AF:

0.00

AC:

AN:

38962

South Asian (SAS)

AF:

0.00

AC:

AN:

59834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

699312

Other (OTH)

AF:

0.00

AC:

AN:

41678

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.67

M_CAP

Benign

0.0080

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

PhyloP100

0.79

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.048

Sift

Benign

0.056

Sift4G

Benign

0.31

Polyphen

0.046

Vest4

0.17

MutPred

0.35

Gain of catalytic residue at L1426 (P = 0.0012)

MVP

0.030

ClinPred

0.26

GERP RS

1.8

Varity_R

0.099

gMVP

0.019

Mutation Taster

=96/4

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.

14-104951177-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over