chr2-241858521-G-GCTGCCCAAACTTTGGGCAGTCAC

Position:

• chr2-241858521-G-GCTGCCCAAACTTTGGGCAGTCAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005018.3(PDCD1):​c.76+241_76+242insGTGACTGCCCAAAGTTTGGGCAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 151,520 control chromosomes in the GnomAD database, including 1,030 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.057 (1030 hom., cov: 33)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.966

Genes affected

PDCD1 (HGNC:8760): (programmed cell death 1) Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-241858521-G-GCTGCCCAAACTTTGGGCAGTCAC is Benign according to our data. Variant chr2-241858521-G-GCTGCCCAAACTTTGGGCAGTCAC is described in ClinVar as [Benign]. Clinvar id is 1234595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1	NM_005018.3	c.76+241_76+242insGTGACTGCCCAAAGTTTGGGCAG		intron_variant		ENST00000334409.10	NP_005009.2
PDCD1	XM_006712573.3	c.76+241_76+242insGTGACTGCCCAAAGTTTGGGCAG		intron_variant			XP_006712636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409.10	c.76+241_76+242insGTGACTGCCCAAAGTTTGGGCAG		intron_variant		1	NM_005018.3	ENSP00000335062.5
PDCD1	ENST00000418831.1	n.76+241_76+242insGTGACTGCCCAAAGTTTGGGCAG		intron_variant		1		ENSP00000390296.1

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8624 AN: 151410 Hom.: 1024 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0653

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

GnomAD4 genome AF: 0.0571 AC: 8653 AN: 151520 Hom.: 1030 Cov.: 33 AF XY: 0.0653 AC XY: 4834 AN XY: 74060

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0679

Alfa AF: 0.0334 Hom.: 25

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35214377; hg19: chr2-242800673;