Variant 14-104938950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_138420.4(AHNAK2):c.16501G>A(p.Val5501Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,613,302 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 11 hom. )

Consequence

AHNAK2
NM_138420.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.594

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063045323).

BP6

Variant 14-104938950-C-T is Benign according to our data. Variant chr14-104938950-C-T is described in ClinVar as [Benign]. Clinvar id is 2644631.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AHNAK2	NM_138420.4 linkuse as main transcript	c.16501G>A	p.Val5501Met	missense_variant	7/7	ENST00000333244.6
AHNAK2	NM_001350929.2 linkuse as main transcript	c.16201G>A	p.Val5401Met	missense_variant	7/7
AHNAK2	XM_024449463.2 linkuse as main transcript	c.16201G>A	p.Val5401Met	missense_variant	7/7
AHNAK2	XM_047430904.1 linkuse as main transcript	c.16201G>A	p.Val5401Met	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHNAK2	ENST00000333244.6 linkuse as main transcript	c.16501G>A	p.Val5501Met	missense_variant	7/7	5	NM_138420.4	P1	Q8IVF2-1
AHNAK2	ENST00000557457.1 linkuse as main transcript	c.1495G>A	p.Val499Met	missense_variant	3/3	1			Q8IVF2-2
AHNAK2	ENST00000555122.1 linkuse as main transcript	n.16629G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00179

AC:

443

AN:

248144

Hom.:

AF XY:

0.00175

AC XY:

236

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.000782

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00336

AC:

4916

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

2381

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000339

Gnomad4 NFE exome

AF:

0.00424

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152218

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00215

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00106

AC:

ESP6500EA

AF:

0.00340

AC:

ExAC

AF:

0.00184

AC:

222

EpiCase

AF:

0.00382

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

AHNAK2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

0.82

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.18

MVP

0.20

ClinPred

0.033

GERP RS

5.2

Varity_R

0.18

gMVP

0.016

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