chr16-69356799-CAAAAAA-C

Variant names:

• chr16-69356799-CAAAAAA-C
• rs372147187
• NM_005652.5:c.*93_*98delTTTTTT

Variant summary

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

The NM_005652.5(TERF2):​c.*93_*98delTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 980,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 0 publications found

Genes affected

TERF2 (HGNC:11729): (telomeric repeat binding factor 2) This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

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_005652.5. 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
	TERF2	NM_005652.5	MANE Select	c.*93_*98delTTTTTT		3_prime_UTR	Exon 10 of 10	NP_005643.2	Q15554-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	ENST00000254942.8	TSL:1 MANE Select	c.*93_*98delTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*93_*98delTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*93_*98delTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 980724 Hom.: 0 AF XY: 0.00000205 AC XY: 1 AN XY: 487194

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21018

American (AMR) AF: 0.00 AC: 0 AN: 19462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15200

East Asian (EAS) AF: 0.00 AC: 0 AN: 30030

South Asian (SAS) AF: 0.00 AC: 0 AN: 52542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 768600

Other (OTH) AF: 0.00 AC: 0 AN: 40996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs372147187; hg19: chr16-69390702;