5-34911779-C-G

Variant names:

• chr5-34911779-C-G
• rs2308957
• NM_002853.4:c.341G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002853.4(RAD1):​c.341G>C​(p.Gly114Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G114D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD1 NM_002853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81
• Publications: 0 publications found

Genes affected

RAD1 (HGNC:9806): (RAD1 checkpoint DNA exonuclease) This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jan 2009]

TTC23L (HGNC:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002853.4. 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
	RAD1	NM_002853.4	MANE Select	c.341G>C	p.Gly114Ala	missense	Exon 4 of 6	NP_002844.1	O60671-1
	RAD1	NR_026591.2		n.390G>C		non_coding_transcript_exon	Exon 3 of 5
	TTC23L	NR_169875.1		n.974-6585C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD1	ENST00000382038.7	TSL:1 MANE Select	c.341G>C	p.Gly114Ala	missense	Exon 4 of 6	ENSP00000371469.2	O60671-1
	RAD1	ENST00000325577.8	TSL:1	n.*25G>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000313467.4	O60671-3
	RAD1	ENST00000325577.8	TSL:1	n.*25G>C		3_prime_UTR	Exon 3 of 5	ENSP00000313467.4	O60671-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.53		Loss of sheet (P = 0.1501)
MVP		0.43
MPC		0.45
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.72
gMVP		0.79
Mutation Taster		=41/59	disease causing

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: rs2308957; hg19: chr5-34911884;