chr2-68157284-C-T

Variant names:

• chr2-68157284-C-T
• rs138076521
• NM_138458.4:c.160G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138458.4(DNAAF10):​c.160G>A​(p.Gly54Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: DNAAF10 NM_138458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25
• Publications: 5 publications found

Genes affected

DNAAF10 (HGNC:25176): (dynein axonemal assembly factor 10) This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ENSG00000273398 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138458.4. 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
	DNAAF10	NM_138458.4	MANE Select	c.160G>A	p.Gly54Arg	missense	Exon 1 of 8	NP_612467.1	Q96MX6-1
	DNAAF10	NM_001256476.2		c.160G>A	p.Gly54Arg	missense	Exon 1 of 7	NP_001243405.1	Q96MX6-2
	DNAAF10	NR_046234.2		n.154+90G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF10	ENST00000295121.11	TSL:1 MANE Select	c.160G>A	p.Gly54Arg	missense	Exon 1 of 8	ENSP00000295121.6	Q96MX6-1
	DNAAF10	ENST00000409164.1	TSL:1	c.160G>A	p.Gly54Arg	missense	Exon 1 of 7	ENSP00000386746.1	Q96MX6-2
	DNAAF10	ENST00000406245.6	TSL:1	c.-121+90G>A		intron	N/A	ENSP00000384518.2	Q8ND98

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000308 AC: 77 AN: 249876 AF XY: 0.000311

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000525

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000370 AC: 541 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.000375 AC XY: 273 AN XY: 727124

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000291 AC: 13 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.000345 AC: 9 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86236

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53376

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000429 AC: 477 AN: 1111898

Other (OTH) AF: 0.000464 AC: 28 AN: 60388

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74458

African (AFR) AF: 0.0000241 AC: 1 AN: 41578

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000560 Hom.: 0

Bravo AF: 0.000257

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000872

EpiControl AF: 0.000889

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.45
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.16	B
Vest4		0.65
MutPred		0.58		Gain of solvent accessibility (P = 0.0306)
MVP		0.66
MPC		0.34
ClinPred		0.32	T
GERP RS		5.8
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.60
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs138076521; hg19: chr2-68384416; COSMIC: COSV99039351; COSMIC: COSV99039351;