rs1028277326

Variant names:

• chr14-69209762-G-A
• rs1028277326
• NM_001193360.2:c.292G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001193360.2(EXD2):​c.292G>A​(p.Glu98Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000403 in 1,487,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: EXD2 NM_001193360.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

Genes affected

EXD2 (HGNC:20217): (exonuclease 3'-5' domain containing 2) Enables 3'-5' exonuclease activity; metal ion binding activity; and protein homodimerization activity. Involved in nucleic acid metabolic process. Located in intermediate filament cytoskeleton; mitochondrial outer membrane; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

GALNT16-AS1 (HGNC:55435): (GALNT16 and EXD2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33986938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193360.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	NM_001193360.2	MANE Select	c.292G>A	p.Glu98Lys	missense	Exon 3 of 10	NP_001180289.1	Q9NVH0-1
	EXD2	NM_001193361.2		c.292G>A	p.Glu98Lys	missense	Exon 2 of 9	NP_001180290.1	Q9NVH0-1
	EXD2	NM_001193362.2		c.292G>A	p.Glu98Lys	missense	Exon 3 of 10	NP_001180291.1	Q9NVH0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	ENST00000685843.1	MANE Select	c.292G>A	p.Glu98Lys	missense	Exon 3 of 10	ENSP00000510642.1	Q9NVH0-1
	EXD2	ENST00000409018.7	TSL:1	c.292G>A	p.Glu98Lys	missense	Exon 2 of 9	ENSP00000387331.3	Q9NVH0-1
	EXD2	ENST00000413191.1	TSL:1	c.-174G>A		5_prime_UTR	Exon 3 of 6	ENSP00000409089.1	C9JLF4

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149320 Hom.: 0 Cov.: 32

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000374 AC: 5 AN: 1338402 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 657676

African (AFR) AF: 0.00 AC: 0 AN: 29680

American (AMR) AF: 0.00 AC: 0 AN: 29840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22670

East Asian (EAS) AF: 0.00 AC: 0 AN: 32818

South Asian (SAS) AF: 0.00 AC: 0 AN: 75532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00000479 AC: 5 AN: 1044606

Other (OTH) AF: 0.00 AC: 0 AN: 54422

GnomAD4 genome AF: 0.00000670 AC: 1 AN: 149320 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72676

African (AFR) AF: 0.00 AC: 0 AN: 40576

American (AMR) AF: 0.00 AC: 0 AN: 14872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 4918

South Asian (SAS) AF: 0.00 AC: 0 AN: 4556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67574

Other (OTH) AF: 0.00 AC: 0 AN: 2070

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.30
Sift	Benign	0.050	D
Sift4G	Benign	0.22	T
Vest4		0.31
MutPred		0.57		Gain of catalytic residue at F102 (P = 5e-04)
MVP		0.71
MPC		0.30
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.33
gMVP		0.65
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1028277326; hg19: chr14-69676479;