Variant rs201127689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138420.4(AHNAK2):c.6509A>T(p.Lys2170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000024 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AHNAK2
NM_138420.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21786895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AHNAK2	NM_138420.4 linkuse as main transcript	c.6509A>T	p.Lys2170Met	missense_variant	7/7	ENST00000333244.6	NP_612429.2
AHNAK2	NM_001350929.2 linkuse as main transcript	c.6209A>T	p.Lys2070Met	missense_variant	7/7		NP_001337858.1
AHNAK2	XM_024449463.2 linkuse as main transcript	c.6209A>T	p.Lys2070Met	missense_variant	7/7		XP_024305231.1
AHNAK2	XM_047430904.1 linkuse as main transcript	c.6209A>T	p.Lys2070Met	missense_variant	7/7		XP_047286860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK2	ENST00000333244.6 linkuse as main transcript	c.6509A>T	p.Lys2170Met	missense_variant	7/7	5	NM_138420.4	ENSP00000353114	P1	Q8IVF2-1
AHNAK2	ENST00000557457.1 linkuse as main transcript	c.-221+4939A>T		intron_variant		1		ENSP00000450998		Q8IVF2-2
AHNAK2	ENST00000555122.1 linkuse as main transcript	n.6637A>T		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000107

AC:

AN:

93190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000309

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000237

AC:

AN:

1179134

Hom.:

Cov.:

104

AF XY:

0.0000272

AC XY:

AN XY:

588122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.0000490

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000225

Gnomad4 NFE exome

AF:

0.0000240

Gnomad4 OTH exome

AF:

0.0000607

GnomAD4 genome

AF:

0.0000107

AC:

AN:

93190

Hom.:

Cov.:

AF XY:

0.0000219

AC XY:

AN XY:

45630

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000309

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

Eigen

Benign

0.13

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.72

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.44

REVEL

Benign

0.11

Sift

Benign

0.091

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.28

MutPred

0.28

Gain of catalytic residue at V2165 (P = 0);

MVP

0.16

ClinPred

0.46

GERP RS

4.0

Varity_R

0.052

gMVP

0.011

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