Variant 14-104951177-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138420.4(AHNAK2):c.4274A>C(p.Asp1425Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,071,286 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D1425G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 6 hom., cov: 18)

Exomes 𝑓: 0.000049 ( 9 hom. )

Consequence

AHNAK2
NM_138420.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.791

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037620366).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AHNAK2	NM_138420.4 linkuse as main transcript	c.4274A>C	p.Asp1425Ala	missense_variant	7/7	ENST00000333244.6
AHNAK2	NM_001350929.2 linkuse as main transcript	c.3974A>C	p.Asp1325Ala	missense_variant	7/7
AHNAK2	XM_024449463.2 linkuse as main transcript	c.3974A>C	p.Asp1325Ala	missense_variant	7/7
AHNAK2	XM_047430904.1 linkuse as main transcript	c.3974A>C	p.Asp1325Ala	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHNAK2	ENST00000333244.6 linkuse as main transcript	c.4274A>C	p.Asp1425Ala	missense_variant	7/7	5	NM_138420.4	P1	Q8IVF2-1
AHNAK2	ENST00000557457.1 linkuse as main transcript	c.-221+2704A>C		intron_variant		1			Q8IVF2-2
AHNAK2	ENST00000555122.1 linkuse as main transcript	n.4402A>C		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

107024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000924

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000551

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000208

AC:

AN:

178006

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

94904

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000487

AC:

AN:

964140

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

478740

show subpopulations

Gnomad4 AFR exome

AF:

0.000503

Gnomad4 AMR exome

AF:

0.000688

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000334

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000720

GnomAD4 genome

AF:

0.000373

AC:

AN:

107146

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

AN XY:

52408

show subpopulations

Gnomad4 AFR

AF:

0.000921

Gnomad4 AMR

AF:

0.000550

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000287

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000164

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.54

M_CAP

Benign

0.0077

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.080

Sift

Benign

0.095

Sift4G

Benign

0.32

Polyphen

0.94

Vest4

0.19

MVP

0.18

ClinPred

0.076

GERP RS

1.8

Varity_R

0.089

gMVP

0.017

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over