Variant 14-104938562-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138420.4(AHNAK2):c.16889G>A(p.Gly5630Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AHNAK2
NM_138420.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.354

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030833483).

BP6

Variant 14-104938562-C-T is Benign according to our data. Variant chr14-104938562-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2259167.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.16889G>A	p.Gly5630Asp	missense_variant	7/7	ENST00000333244.6
AHNAK2	NM_001350929.2 linkuse as main transcript	c.16589G>A	p.Gly5530Asp	missense_variant	7/7
AHNAK2	XM_024449463.2 linkuse as main transcript	c.16589G>A	p.Gly5530Asp	missense_variant	7/7
AHNAK2	XM_047430904.1 linkuse as main transcript	c.16589G>A	p.Gly5530Asp	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHNAK2	ENST00000333244.6 linkuse as main transcript	c.16889G>A	p.Gly5630Asp	missense_variant	7/7	5	NM_138420.4	P1	Q8IVF2-1
AHNAK2	ENST00000557457.1 linkuse as main transcript	c.1883G>A	p.Gly628Asp	missense_variant	3/3	1			Q8IVF2-2
AHNAK2	ENST00000555122.1 linkuse as main transcript	n.17017G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247704

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.00

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

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0050

DANN

Benign

0.77

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.34

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.0090

Sift

Benign

0.96

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.011

.;B

Vest4

0.040

MVP

0.014

ClinPred

0.032

GERP RS

-4.5

Varity_R

0.032

gMVP

0.0085

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