14-104938523-C-T

Variant names:

• chr14-104938523-C-T
• rs200328056
• NM_138420.4:c.16928G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138420.4(AHNAK2):​c.16928G>A​(p.Gly5643Asp) 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. 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: not found (cov: 32)
• Consequence: AHNAK2 NM_138420.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17059213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHNAK2	NM_138420.4	c.16928G>A	p.Gly5643Asp	missense_variant	Exon 7 of 7	ENST00000333244.6	NP_612429.2
AHNAK2	NM_001350929.2	c.16628G>A	p.Gly5543Asp	missense_variant	Exon 7 of 7		NP_001337858.1
AHNAK2	XM_024449463.2	c.16628G>A	p.Gly5543Asp	missense_variant	Exon 7 of 7		XP_024305231.1
AHNAK2	XM_047430904.1	c.16628G>A	p.Gly5543Asp	missense_variant	Exon 7 of 7		XP_047286860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHNAK2	ENST00000333244.6	c.16928G>A	p.Gly5643Asp	missense_variant	Exon 7 of 7	5	NM_138420.4	ENSP00000353114.4
AHNAK2	ENST00000557457.1	c.1922G>A	p.Gly641Asp	missense_variant	Exon 3 of 3	1		ENSP00000450998.1
AHNAK2	ENST00000555122.1	n.17056G>A		non_coding_transcript_exon_variant	Exon 6 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.17
Sift	Benign	0.045	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	.;D
Vest4		0.17
MutPred		0.47		.;Gain of catalytic residue at L5644 (P = 0);
MVP		0.072
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.073
gMVP		0.027

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

Other links and lift over

dbSNP: rs200328056; hg19: chr14-105404860;