chr19-45352004-G-T

Position:

• chr19-45352004-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000391945.10(ERCC2):​c.2190+205C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,048 control chromosomes in the GnomAD database, including 23,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.52 (23713 hom., cov: 32)
• Consequence: ERCC2 ENST00000391945.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212

Genes affected

ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 19-45352004-G-T is Benign according to our data. Variant chr19-45352004-G-T is described in ClinVar as [Benign]. Clinvar id is 1230280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.2190+205C>A		intron_variant		ENST00000391945.10	NP_000391.1
ERCC2	XM_011526611.3	c.2112+205C>A		intron_variant			XP_011524913.1
ERCC2	XR_001753633.3	n.2223+205C>A		intron_variant, non_coding_transcript_variant
ERCC2	XR_007066680.1	n.2145+205C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.2190+205C>A		intron_variant		1	NM_000400.4	ENSP00000375809	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78652 AN: 151930 Hom.: 23662 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.518 AC: 78749 AN: 152048 Hom.: 23713 Cov.: 32 AF XY: 0.517 AC XY: 38389 AN XY: 74320

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.470

Alfa AF: 0.281 Hom.: 611

Bravo AF: 0.528

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs238418; hg19: chr19-45855262;