7-44210266-G-A

Variant names:

• chr7-44210266-G-A
• rs2331003
• NM_006555.4:c.460-757G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006555.4(YKT6):​c.460-757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,142 control chromosomes in the GnomAD database, including 53,549 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53549 hom., cov: 31)
• Consequence: YKT6 NM_006555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 4 publications found

Genes affected

YKT6 (HGNC:16959): (YKT6 v-SNARE homolog) This gene product is one of the SNARE recognition molecules implicated in vesicular transport between secretory compartments. It is a membrane associated, isoprenylated protein that functions at the endoplasmic reticulum-Golgi transport step. This protein is highly conserved from yeast to human and can functionally complement the loss of the yeast homolog in the yeast secretory pathway. [provided by RefSeq, Jul 2008]

CAMK2B (HGNC:1461): (calcium/calmodulin dependent protein kinase II beta) The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

CAMK2B Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 40

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• intellectual disability, autosomal dominant 54

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YKT6	NM_006555.4	c.460-757G>A		intron_variant	Intron 5 of 6	ENST00000223369.3	NP_006546.1
YKT6	NM_001410874.1	c.460-757G>A		intron_variant	Intron 5 of 7		NP_001397803.1
YKT6	NM_001363678.2	c.460-1981G>A		intron_variant	Intron 5 of 5		NP_001350607.1
YKT6	XM_054328423.1	c.460-757G>A		intron_variant	Intron 5 of 6		XP_054184398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YKT6	ENST00000223369.3	c.460-757G>A		intron_variant	Intron 5 of 6	1	NM_006555.4	ENSP00000223369.2

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127388 AN: 152022 Hom.: 53501 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.808

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.838 AC: 127495 AN: 152142 Hom.: 53549 Cov.: 31 AF XY: 0.841 AC XY: 62522 AN XY: 74376

African (AFR) AF: 0.901 AC: 37397 AN: 41516

American (AMR) AF: 0.798 AC: 12195 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2728 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4268 AN: 5148

South Asian (SAS) AF: 0.790 AC: 3803 AN: 4812

European-Finnish (FIN) AF: 0.870 AC: 9221 AN: 10598

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55263 AN: 67994

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.829 Hom.: 13962

Bravo AF: 0.833

Asia WGS AF: 0.808 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.32
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2331003; hg19: chr7-44249865;