chr10-125836726-C-A

Variant names:

• chr10-125836726-C-A
• NM_018180.3:c.2193G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018180.3(DHX32):​c.2193G>T​(p.Glu731Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E731Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DHX32 NM_018180.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.716
• Publications: 0 publications found

Genes affected

DHX32 (HGNC:16717): (DEAH-box helicase 32 (putative)) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates 2 transcript variants, but the full length nature of one of the variants has not been defined. [provided by RefSeq, Jul 2008]

BCCIP (HGNC:978): (BRCA2 and CDKN1A interacting protein) This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. This protein has also been implicated in the regulation of BRCA2 and RAD51 nuclear focus formation, double-strand break-induced homologous recombination, and cell cycle progression. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06517142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018180.3. 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
	DHX32	NM_018180.3	MANE Select	c.2193G>T	p.Glu731Asp	missense	Exon 11 of 11	NP_060650.2
	BCCIP	NM_016567.4		c.774+2780C>A		intron	N/A	NP_057651.1	Q9P287-2
	BCCIP	NM_078469.3		c.774+2780C>A		intron	N/A	NP_510869.1	Q9P287-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX32	ENST00000284690.4	TSL:1 MANE Select	c.2193G>T	p.Glu731Asp	missense	Exon 11 of 11	ENSP00000284690.3	Q7L7V1-1
	DHX32	ENST00000368721.5	TSL:1	c.1065G>T	p.Glu355Asp	missense	Exon 8 of 8	ENSP00000357710.1	X6R717
	BCCIP	ENST00000368759.5	TSL:1	c.774+2780C>A		intron	N/A	ENSP00000357748.5	Q9P287-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4
DANN	Benign	0.96
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.72
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.089
Sift	Benign	0.46	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.11		Gain of helix (P = 0.062)
MVP		0.31
MPC		0.20
ClinPred		0.045	T
GERP RS		-4.0
Varity_R		0.031
gMVP		0.38
Mutation Taster		=92/8	polymorphism

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

hg19: chr10-127525295;